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. 2008 Dec;52(12):4388-99.
doi: 10.1128/AAC.00381-08. Epub 2008 Sep 8.

In vitro activity of doripenem, a carbapenem for the treatment of challenging infections caused by gram-negative bacteria, against recent clinical isolates from the United States

Chris M Pillar  1 , Mohana K Torres, Nina P Brown, Dineshchandra Shah, Daniel F Sahm
Affiliations

In vitro activity of doripenem, a carbapenem for the treatment of challenging infections caused by gram-negative bacteria, against recent clinical isolates from the United States

Chris M Pillar et al. Antimicrob Agents Chemother. 2008 Dec.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
MIC distributions and cumulative susceptibilities of doripenem and comparator MICs against Enterobacteriaceae (n = 5,029).
FIG. 2.
FIG. 2.
MIC distributions and cumulative susceptibilities of doripenem and comparator MICs against P. aeruginosa (n = 875).
FIG. 3.
FIG. 3.
MIC distributions and cumulative susceptibilities of doripenem and comparator MICs against Acinetobacter spp. (n = 5,029).
See this image and copyright information in PMC

References

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