Vol.53 No.S-1 July 2005
In vitro postantibiotic effect and in vivo antimicrobial activity of doripenem, a new carbapenem
Department of Infectious Diseases, Tokyo Women's Medical University,
8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan
Abstract
We evaluated the in vitro postantibiotic effect and in vivo antimicrobial activity of doripenem (DRPM), a new carbapenem, against Staphylococcus aureus Smith, Klebsiella pneumoniae BK, Escherichia coli ATCC25922, and Pseudomonas aeruginosa ATCC27853. PAE was determined by exposing the organism for 2 hours to DRPM, imipenem (IPM), panipenem (PAPM), and ceftazidime (CAZ) at concentrations of 4 times the MIC. For in vivo study, a neutropenic mouse-thigh infection model was used. Neutropenia was induced by injection with 150 mg/kg of cyclophosphamide ip 4 days and 100 mg/kg 1 day, before infection. The time when viable cell number return to the level at drug administration was defined as the effective regrowth time (ERT).
In vitro PAE of DRPM against S. aureus Smith, was 1.9 h, IPM 1.6 h, PAPM 1.8 h, and CAZ 1.8 h. Those against K. pneumoniae BK were 0.3 h, 0.5 h, 0.4 h, and 0.1 h. Those against E. coli ATCC25922 were 0.5 h, 0.6 h, 0.6 h and 0.4 h. Those against P. aeruginosa ATCC27853 were 1.8 h, 1.0 h, 1.0 h, and -0.3 h.
In vivo ERT of DRPM with dose of 50 mg/kg against S. aureus Smith was 7.8 h, IPM/cilastatin (CS) 12.3 h, and PAPM/betamipron (BP) 10.8 h. Those of S-4661, IPM/CS, PAPM/BP, meropenem (MEPM) and CAZ against K. pneumoniae BK with dose of 50 mg/kg were 5.0 h, 5.5 h, 4.3 h, 5.0 h, and 6.0 h. Those against P. aeruginosa ATCC27853 with dose of 100 mg/kg were 8.0 h, 9.8 h, 8.3 h, 5.3 h and 2.7 h.
In vitro PAEs of DRPM against S. aureus Smith, K. pneumoniae BK, and E. coli ATCC25922 were almost the same as other carbapenems and the longest of all against P. aeruginosa was ATCC27853. In vivo activity DRPM against K. pneumoniae BK and P. aeruginosa ATCC27853 was almost the same as other carbapenems, but less potent against S. aureus Smith than IPM/CS and PAPM/BP.
Key word
doripenem, postantibiotic effect, effective regrowth time
Received
March 2, 2005
Accepted
March 9, 2005
Jpn. J. Chemother. 53 (S-1): 52-56, 2005
