Doripenem

Carbapenems play a significant role in the current antibiotic armamentarium. Doripenem is the newest carbapenem to be commercially released. Its antimicrobial spectrum more closely resembles those of meropenem and imipenem than that of ertapenem. Thus, it has significant in vitro activity against streptococci, methicillin-susceptible staphylococci, Enterobacteriaceae (including extended-spectrum beta-lactamase-producing strains), Pseudomonas aeruginosa, Acinetobacter species, and Bacteroides fragilis. Doripenem does not have clinically useful activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and the majority of gram-negative bacilli that are resistant to meropenem or imipenem. In vitro, resistant P. aeruginosa mutants appear to be harder to select with doripenem than with other carbapenems. Doripenem has been approved for use in treatment of complicated intra-abdominal infection and complicated urinary tract infection. Studies of hospital-acquired pneumonia have also been completed, including one that used a 4-h infusion to enhance the pharmacodynamic profile. In vitro, doripenem lacks the propensity to cause seizures, and a low risk of seizures has been demonstrated in clinical studies. Currently unanswered questions regarding doripenem include the utility and dosing in neonatal, pediatric, and cystic fibrosis populations and specific dosage recommendations for patients receiving hemodialysis, peritoneal dialysis, or continuous renal replacement therapies. The longevity of doripenem will depend on our ability to curtail the spread of carbapenem-resistant organisms, which are already a significant problem at some institutions.