In vitro pharmacodynamic studies of L-749,345 in comparison with imipenem and ceftriaxone against gram-positive and gram-negative bacteria

Antimicrob Agents Chemother. 1998 Sep;42(9):2365-70. doi: 10.1128/AAC.42.9.2365.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Ceftriaxone / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Imipenem / pharmacology*
  • Methicillin Resistance
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • L 749345
  • Imipenem
  • Ceftriaxone