OBJECTIVES: To evaluate development of resistance to the piperacillin/BLI-489 combination. METHODS: BLI-489 was used at a constant concentration of 4 mg/L. Spontaneous mutation frequency was measured on piperacillin/BLI-489-containing agar plates. Five beta-lactamase-producing strains were exposed to a serial dilution of piperacillin/BLI-489, and the highest concentration allowing growth was used to inoculate subsequent serial passage for 10 days. Mutation stability was monitored in drug-free medium for 10 days. RESULTS: Escherichia coli (OXA-3, OXA-7, ACT-1, SHV-1 or none), Salmonella enterica serovar Typhimurium (CTX-M-5), Klebsiella pneumoniae (SHV-1 and SHV-5) and Enterobacter cloacae (AmpC) had a spontaneous mutation frequency of < or =1.0 x 10(-9). Two AmpC-producing Pseudomonas aeruginosa strains had a mutation frequency of 6.52 x 10(-6) and 1.0 x 10(-7); a beta-lactamase-negative P. aeruginosa strain had a mutation frequency of 2.68 x 10(-8). The mutant prevention concentration (MPC) was < or =32 mg/L. During serial passages, the MIC increased 64- and 128-fold for S. enterica serovar Typhimurium (CTX-M-5) and E. cloacae (AmpC), respectively, to > or =512 mg/L. The MIC reverted to < or =64 mg/L after serial passages in drug-free medium. The MICs increased only 4-fold for K. pneumoniae (SHV-1 and SHV-5), E. coli (OXA-3) and E. coli (SHV-1). CONCLUSIONS: Piperacillin/BLI-489 demonstrated a low probability of spontaneous resistance development in vitro for all of the strains tested with the exception of P. aeruginosa. The MPC value for all strains was < or =32 mg/L. Resistance developed during serial passage for two of the five strains tested; however, this resistance phenotype was unstable as MIC values reverted to < or =64 mg/L after propagation in drug-free medium.
OBJECTIVES: To evaluate development of resistance to the piperacillin/BLI-489 combination. METHODS:BLI-489 was used at a constant concentration of 4 mg/L. Spontaneous mutation frequency was measured on piperacillin/BLI-489-containing agar plates. Five beta-lactamase-producing strains were exposed to a serial dilution of piperacillin/BLI-489, and the highest concentration allowing growth was used to inoculate subsequent serial passage for 10 days. Mutation stability was monitored in drug-free medium for 10 days. RESULTS:Escherichia coli (OXA-3, OXA-7, ACT-1, SHV-1 or none), Salmonella enterica serovar Typhimurium (CTX-M-5), Klebsiella pneumoniae (SHV-1 and SHV-5) and Enterobacter cloacae (AmpC) had a spontaneous mutation frequency of < or =1.0 x 10(-9). Two AmpC-producing Pseudomonas aeruginosa strains had a mutation frequency of 6.52 x 10(-6) and 1.0 x 10(-7); a beta-lactamase-negative P. aeruginosa strain had a mutation frequency of 2.68 x 10(-8). The mutant prevention concentration (MPC) was < or =32 mg/L. During serial passages, the MIC increased 64- and 128-fold for S. enterica serovar Typhimurium (CTX-M-5) and E. cloacae (AmpC), respectively, to > or =512 mg/L. The MIC reverted to < or =64 mg/L after serial passages in drug-free medium. The MICs increased only 4-fold for K. pneumoniae (SHV-1 and SHV-5), E. coli (OXA-3) and E. coli (SHV-1). CONCLUSIONS:Piperacillin/BLI-489 demonstrated a low probability of spontaneous resistance development in vitro for all of the strains tested with the exception of P. aeruginosa. The MPC value for all strains was < or =32 mg/L. Resistance developed during serial passage for two of the five strains tested; however, this resistance phenotype was unstable as MIC values reverted to < or =64 mg/L after propagation in drug-free medium.
Authors: Jared L Crandon; Virna J Schuck; Mary Anne Banevicius; Marie-Eve Beaudoin; Wright W Nichols; M Angela Tanudra; David P Nicolau Journal: Antimicrob Agents Chemother Date: 2012-09-17 Impact factor: 5.191
Authors: Samuel T Cahill; Ricky Cain; David Y Wang; Christopher T Lohans; David W Wareham; Henry P Oswin; Jabril Mohammed; James Spencer; Colin W G Fishwick; Michael A McDonough; Christopher J Schofield; Jürgen Brem Journal: Antimicrob Agents Chemother Date: 2017-03-24 Impact factor: 5.191