title: In vitro pharmacodynamic studies of L-749,345 in comparison with imipenem and ceftriaxone against gram-positive and gram-negative bacteria.
abstract: L-749,345 is a new parenteral carbapenem with a very long half-life similar to that of ceftriaxone. The aim of the present study was to investigate different pharmacodynamic parameters of L-749,345 in comparison with those of ceftriaxone and imipenem. The following studies were performed: (i) comparative studies of the MICs of L-749, 345, imipenem, and ceftriaxone for 70 strains of gram-positive and gram-negative bacteria; (ii) comparative studies of the rate of killing of gram-positive and gram-negative bacteria by L-749,345, imipenem, and ceftriaxone; (iii) studies of the postantibiotic effects of L-749,345, imipenem, and ceftriaxone; and (iv) studies of the postantibiotic sub-MIC effects of L-749,345, imipenem, and ceftriaxone. Significantly lower MICs of L-749,345 compared with those of ceftriaxone were found for all gram-negative organisms except Haemophilus influenzae. The MICs of L-749,345 were similar to those of imipenem for all organisms except Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, for which the MICs of L-749,345 were higher. A concentration-dependent killing of methicillin-resistant S. aureus but not methicillin-susceptible strains was noted for both L-749,345 and imipenem. All three of the investigated drugs exhibited a postantibiotic effect against the gram-positive strains but exhibited no postantibiotic effect against the gram-negative strains.
authors.affiliation: Antibiotic Research Unit, Department of Infectious Diseases and Clinical Microbiology, University Hospital, Uppsala, Sweden. Inga.Odenholt@infektion.uas
authors.forename: I
authors.initials: I
authors.lastname: Odenholt
authors.forename: E
authors.initials: E
authors.lastname: Löwdin
authors.forename: O
authors.initials: O
authors.lastname: Cars
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D015378:Imipenem / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; C108047:L 749345; D015378:Imipenem; D002443:Ceftriaxone