Antimicrobial activity of doripenem tested against prevalent Gram-positive pathogens: results from a global surveillance study (2003–2007)

Doripenem is a broad-spectrum parenteral carbapenem recently approved in the United States for treatment of complicated urinary tract and intra-abdominal infections. Although pronounced doripenem antimicrobial activity against various Gram-negative pathogens, including anaerobes, has been confirmed, limited information has been forthcoming on the activity of this agent against leading Gram-positive species. We evaluated the activity of doripenem using reference broth microdilution procedures against a large collection of staphylococci, enterococci, and streptococci collected as part of a global (North America, 43.0%; Latin America, 11.7%; Europe, 31.3%; and Asia-Pacific, 14.0%) Doripenem Surveillance Program for the years 2003 to 2007. Doripenem was confirmed to be highly active against oxacillin-susceptible Staphylococcus aureus (22 389 isolates) and coagulase-negative staphylococci (2444 isolates; MIC90 values, ≤0.06 μg/mL), with no differences noted between geographic regions. Against Enterococcus faecalis (8714 isolates), doripenem displayed modest activity (MIC50, 4 μg/mL) but was largely inactive against Enterococcus faecium (4233 isolates). Although not currently approved for treatment of respiratory tract infections in the United States, doripenem was highly active against Streptococcus pneumoniae (10 260 isolates; MIC90, 0.5 μg/mL) and 2-fold more active than either ceftriaxone or cefepime. Doripenem activity was even more noteworthy against β-hemolytic streptococci (4598 isolates; MIC90, ≤0.06 μg/mL, similar to that of penicillin) and viridans group streptococci (1887 isolates; MIC90, 0.25 μg/mL). Doripenem appears broadly active in vitro against Gram-positive pathogens, a potency similar to that of other carbapenems, a distinct advantage that complements other attributes including β-lactamase and dehydropeptidase stability and activity against emerging multidrug-resistant Gram-negative pathogens.