An in vitro evaluation of HRE 664, a novel penem antibiotic

HRE 664 is a novel parenteral penem with a broad antimicrobial spectrum. In this study, HRE 664 inhibited 90% of Enterobacteriaceae at less than or equal to 2.0 micrograms/ml, Haemophilus influenzae and Neisseria gonorrhoeae at less than or equal to 0.5 microgram/ml, oxacillin-susceptible staphylococci at less than or equal to 0.13 microgram/ml, oxacillin-resistant staphylococci at less than or equal to 8.0 micrograms/ml, enterococci at less than or equal to 8.0 micrograms/ml, and streptococci at less than or equal to 0.13 microgram/ml. All strains of Pseudomonas aeruginosa were resistant (MICs were greater than 32 micrograms/ml). HRE 664 exhibited a minimal inoculum effect and good bactericidal activity with all organisms tested except an oxacillin-resistant Staphylococcus aureus. With the latter, there was a marked inoculum effect and no on-scale bactericidal endpoints. No measurable hydrolysis of HRE 664 occurred with any of the five Gram-negative bacterial beta-lactamases tested. When stored at -20 degrees C, HRE 664 showed no significant loss of activity for up to 6 wk, but detectable deterioration occurred thereafter. At -60 degrees C, no loss in HRE 664 potency was observed for up to 12 wk. Proposed HRE 664 MIC quality control parameters are: 0.03-0.13 microgram/ml for S. aureus ATCC 29213, 0.25-1.0 micrograms/ml for Escherichia coli 25922, and 2.0-8.0 micrograms/ml for Enterococcus faecalis ATCC 29212.