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Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)
T R Fritsche1, M G Stilwell, R N Jones
1JMI Laboratories, North Liberty, IA, USA. thomas-fritsche@jmilabs.com
Abstract:
The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and beta-haemolytic streptococci (885, 140 and 397 isolates; MIC(90)s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all beta-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and
Insights
Doripenem, a new carbapenem antibiotic, shows high potency and broad-spectrum activity against many common bacterial pathogens. It demonstrates advantages over other carbapenems, particularly against Gram-negative bacteria and in beta-lactamase stability.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Carbapenem antibiotics are crucial for treating severe bacterial infections.
- Emerging antibiotic resistance necessitates continuous evaluation of existing and novel antimicrobial agents.
- Doripenem is a novel carbapenem antibiotic undergoing clinical development.
Purpose of the Study:
- To evaluate the spectrum of activity and potency of doripenem against a large collection of recent clinical bacterial isolates.
- To compare doripenem's antimicrobial activity with other established carbapenem and beta-lactam antibiotics.
- To assess doripenem's efficacy against resistant bacterial strains, including those producing extended-spectrum beta-lactamases (ESBLs).
Main Methods:
- A total of 16,008 clinical bacterial isolates were collected internationally in 2003.
- Antimicrobial susceptibility testing was performed using reference broth microdilution methods.
- Minimum inhibitory concentrations (MICs) were determined, and MIC90 values were calculated for various bacterial species.
Main Results:
- Doripenem exhibited high activity against Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, and viridans group streptococci.
- It demonstrated potent activity against Enterobacteriaceae, including ESBL-producing Escherichia coli and Klebsiella pneumoniae, outperforming imipenem.
- Doripenem showed significant activity against Pseudomonas aeruginosa, Acinetobacter spp., Haemophilus influenzae, and Moraxella catarrhalis, with notable beta-lactamase stability.
Conclusions:
- Doripenem possesses a broad spectrum of activity and high potency against a wide range of clinically relevant bacteria.
- It offers potential advantages in potency, spectrum, and beta-lactamase stability compared to some currently used carbapenems.
- Doripenem represents a promising therapeutic option for managing nosocomial infections.
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