Affiliation:
1. Eurofins Medinet Inc., Herndon, Virginia
Abstract
ABSTRACT
Doripenem, a 1β-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 (μg/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, ≤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 β-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 β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against
P. aeruginosa
regardless of β-lactam resistance.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
57 articles.
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