title: Comparative in vitro pharmacodynamics of BO-2727, meropenem and imipenem against Gram-positive and Gram-negative bacteria.
abstract: OBJECTIVE: To investigate and compare the in vitro pharmacodynamics of three carbapenems: imipenem, meropenem and BO-2727. METHODS: The following studies were performed: (1) comparative studies of the rate of killing of the three carbapenems of reference strains of Gram-positive and Gram-negative bacteria at a concentration corresponding to the 1-h serum level following 500 mg intravenously in humans; (2) comparative studies of the rate of killing of BO-2727, meropenem and imipenem at different antibiotic concentrations of reference strains of Gram-positive and Gram-negative bacteria; (3) comparative studies of the rate of killing of BO-2727, meropenem and imipenem of bacteria which are phenotypically tolerant; (4) studies of the postantibiotic effect of BO-2727 using viable counts and optical density; (5) studies of the postantibiotic sub-MIC effect (PA SME) of BO-2727 using optical density. RESULTS: No difference in killing rate was noted between the three carbapenems, and there was no concentration-dependent killing of the Gram-negative strains after 6 h. A pronounced paradoxical effect was seen against Staphylococcus aureus. All three antibiotics were able to kill phenotypically tolerant bacteria. Only very short or no postantibiotic effect of BO-2727 was found against the investigated strains. Very long PA SMEs were noted for the Gram-negative strains, although there was a pronounced variation for the different strains of Pseudomonas aeruginosa. CONCLUSION: There was no significant difference between the studied carbapenems in their pharmacodynamic properties. All three antibiotics acted similarly to other beta-lactam antibiotics.
authors.affiliation: Antibiotic Research Unit, Department of Infectious Diseases and Clinical Microbiology, University Hospital, Uppsala, Sweden.
authors.forename: Inga
authors.initials: I
authors.lastname: Odenholt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Löwdin
authors.forename: Otto
authors.initials: O
authors.lastname: Cars