Newer carbapenems for urinary tract infections

Four carbapenems have been available clinically in Japan. These are imipenem/cilastatin (IMIP/CS) and panipenem/ betamipron (PANI/BP) of the older compounds and newer carbapenems such as biapem (BIAP) and meropenem (MERO). The latter compounds are relatively stable to dehydropeptidase-1 (DHP-1) and have been reported to have higher antimicrobial activities compared to the earlier carbapenems. The antimicrobial activity of these four carbapenems against fresh urinary isolates showed high activities against Enterobacteriacae such as Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Escherichia coli containing the class C-beta-lactamase- and extended spectrum beta-lactamase (ESBL)-producing strains compared to piperacillin (PIPC) and ceftazidime (CTAZ). Against Pseudomonas aeruginosa, the carbapenems, with the exception of panipenem showed strong antimicrobial activities compared to PIPC and CTAZ. High activities were also seen against Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis, but methicillin-resistant strains were not affected. The first generation carbapenems showed better activity against E. faecalis than newer carbapenems. All four carbapenems were similar in clinical effectiveness in double blind trials for complicated urinary tract infections (UTIs). However, PANI/BP is less effective in UTIs caused by P. aeruginosa than IMIP/CS. MERO showed better eradication rate of P. aeruginosa than IMIP/CS. Retrospective analysis of treated cases using carbapenems showed a rapid defervescence in the treatment of febrile complicated UTIs, which were mainly caused by mixed infection of Gram-negative and Gram-positive bacteria, especially those involving P. aeruginosa and E. faecalis.