Doripenem exhibits broad-spectrum antimicrobial activity against a variety of bacterial strains, including multidrug-resistant pathogens. It demonstrates effectiveness against Acinetobacter baumannii (including isolates producing OXA-23, IMP-4, and KPC beta-lactamases), Pseudomonas aeruginosa (including oprD-deficient and multidrug-resistant isolates), Escherichia coli, Klebsiella pneumoniae (including ESBL- and carbapenemase-producing strains), Clostridium difficile, and several anaerobes such as Bacteroides and Fusobacterium species. The MIC values for Doripenem vary widely depending on the bacterial strain, ranging from as low as 0.015 μg/mL to greater than 128 μg/mL.
Doripenem has been shown to exhibit significant bactericidal activity, with high killing rates at MIC and 2xMIC levels for various bacterial strains. It also demonstrates potent inhibition of penicillin-binding proteins (PBPs) in E. coli and P. aeruginosa, and activity against enzymes such as CTX-M-15, CTX-M-71, and Mycobacterium tuberculosis LdtMt1. Moreover, the compound displays time-dependent pharmacokinetics, with favorable T>MIC values and pharmacokinetic parameters, including distribution, clearance, and half-life, in both healthy individuals and patients with renal impairment.
In addition to antibacterial properties, Doripenem also shows some antiviral activity against SARS-CoV-2, inhibiting the virus-induced cytotoxicity in cell assays. The compound has demonstrated minimal liver toxicity but is associated with various adverse effects like gastrointestinal symptoms and headaches when administered intravenously. Overall, Doripenem holds promise as an antimicrobial agent, especially for treating severe and multidrug-resistant bacterial infections, though careful monitoring during treatment is advised..
Note: Summary generated by AI. Data source: ChEMBL 