CL 188,624, CL 190,294, and CL 191,121 are novel aminomethyl tetrahydrofura
nyl (THF)-1 beta-methylcarbapenems. The in vitro antibacterial activities o
f these THF carbapenems were evaluated and compared with those of biapenem,
imipenem, and meropenem against 554 recent clinical isolates obtained from
geographically distinct medical centers across North America. The. antibac
terial activities of the THF carbapenems were equivalent to that of biapene
m, and the THF carbapenems were slightly more active than imipenem and less
active than meropenem against most of the members of the family Enterobact
eriaceae but lacked significant activity against Pseudomonas isolates. In g
eneral, CL 191,121 was two- to fourfold more active than CL 188,624 and CL
190,294 against the staphylococcal and enterococcal isolates tested. CL 191
,121 was twofold less active than imipenem against methicillin-susceptible
staphylococci and was as activity as imipenem against Enterococcus faecalis
isolates. Biapenem and meropenem were two- and fourfold less active than C
L 191,121, respectively, against the methicillin-susceptible staphylococci
and E. faecalis, All the carbapenems displayed equivalent good activities a
gainst the streptococci, Biapenem was slightly more active than the other c
arbapenems against Bacteroides fragilis isolates. Time-kill curve studies d
emonstrated that the TRF carbapenems were bactericidal in 6 h against Esche
richia call and Staphylococcus aureus isolates. The postantibiotic effect e
xerted by CL 191,121 was comparable to or slightly longer than that of imip
enem against isolates of S. aureus, E. coli, and Klebsiella pneumoniae.