Abstract:
BACKGROUND: In 2008, ceftobiprole was approved by Health
Canada for the treatment of patients with complicated skin and skin
structure infections including diabetic foot infections; approval of
ceftobiprole by the United States Food and Drug Administration is
pending. Doripenem is currently under review by Health Canada and
was approved by the United States Food and Drug Administration in
2007 for the treatment of patients with complicated intra-abdominal
infections and complicated urinary tract infections, including pyelonephritis.
OBJECTIVES: To determine the in vitro activities of ceftobiprole and
doripenem using a collection of frequently isolated aerobic and facultative
bacteria cultured from patient blood, urine, respiratory and
wound specimens in 12 Canadian hospitals in 2007.
MEtHODS: Isolates were tested for their susceptibility to a panel of
antimicrobial agents using the Clinical and Laboratory Standards
Institute broth microdilution method.
RESULTS: Ceftobiprole inhibited all isolates of methicillin-resistant
Staphylococcus aureus (n=385), methicillin-resistant Staphylococcus
epidermidis (n=20), methicillin-susceptible S aureus (n=1095) and
methicillin-susceptible S epidermidis (n=108) at a minimum inhibitory
concentration (MIC) of 2 μg/mL or less; all isolates of Streptococcus
pyogenes (n=105) were inhibited by ceftobiprole at 0.06 μg/mL or less.
All isolates of S aureus (MIC 4 μg/mL or less) and S pyogenes (MIC
0.5 μg/mL or less) tested were susceptible to ceftobiprole. Greater than
99% of extended-spectrum beta-lactamase (ESBL)-negative Escherichia
coli (n=1528) and Klebsiella pneumoniae (n=436) were susceptible to
ceftobiprole (MIC 1 μg/mL or less); against other genera/species of
Enterobacteriaceae, susceptibility to ceftobiprole ranged from 80.7%
for Enterobacter cloacae (n=166) to 99.2% for Proteus mirabilis (n=119).
Ceftobiprole was less active against Pseudomonas aeruginosa (n=633)
(90% of isolates inhibited at a concentration of 32 μg/mL [MIC90])
than Enterobacteriaceae. Doripenem inhibited 90% of isolates of E coli
(n=1577) and K pneumoniae (n=456), including ESBL-producing isolates
(n=69), and E cloacae at a concentration of 0.06 μg/mL or less;
doripenem and meropenem had MIC90s of 8 μg/mL for the isolates of
P aeruginosa tested. Doripenem demonstrated in vitro activity indistinguishable
from that of meropenem against Gram-positive pathogens.
CONCLUSIONS: All isolates of methicillin-resistant S aureus tested
were susceptible to ceftobiprole (MIC 4 μg/mL or less), differentiating
it from any other currently marketed beta-lactam. Doripenem demonstrated
potent activity (MIC90 0.5 μg/mL or less) against all isolates of
Enterobacteriaceae tested, including ESBL-producing E coli and
K pneumoniae, and as potent activity as meropenem (MIC90 8 μg/mL)
against P aeruginosa. The current study demonstrated both ceftobiprole
and doripenem to be promising broad-spectrum antibacterial agents.
