Doripenem, a
1beta-methylcarbapenem, is a broad-spectrum
antibiotic approved for the treatment of complicated urinary tract and complicated
intra-abdominal infections. An indication for
hospital-acquired pneumonia including
ventilator-associated pneumonia is pending. The current study examined the activity of
doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis.
Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus,
coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (microg/ml) were established by broth microdilution. By MIC(90),
doripenem was comparable to
imipenem and
meropenem in activity against S. aureus (
methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (
penicillin susceptible, < or =0.015; resistant, 1). Against
ceftazidime-susceptible Enterobacteriaceae, the MIC(90) of
doripenem (0.12) was comparable to that of
meropenem (0.12) and superior to that of
imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated
carbapenems. The activity of
doripenem was not notably altered against
ceftazidime-nonsusceptible or extended-spectrum
beta-lactamase screen-positive Enterobacteriaceae.
Doripenem was the most potent
carbapenem tested against P. aeruginosa (MIC(90)/% susceptibility [%S]:
ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S;
imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against
imipenem-susceptible Acinetobacter spp.,
doripenem (MIC(90) = 2, 89.1%S) was twice as active by MIC(90) as were
imipenem and
meropenem. Overall,
doripenem potency was comparable to those of
meropenem and
imipenem against gram-positive cocci and
doripenem was equal or superior in activity to
meropenem and
imipenem against Enterobacteriaceae, including
beta-lactam-nonsusceptible isolates.
Doripenem was the most active
carbapenem tested against P. aeruginosa regardless of beta-lactam resistance.