What's new and not so new on the antimicrobial horizon?
Despite increasing antimicrobial resistance and multiple drug resistance in clinical isolates of both Gram-positive and Gram-negative bacteria, there are few novel antimicrobial agents in development. The few new agents that have been recently licensed have tended to have narrow spectra of activity, focused on Gram-positive pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA). This situation is rightly causing concern among clinicians and public health authorities worldwide. This article reviews available data on three new antibacterials currently in development. The cephalosporin ceftobiprole is active against MRSA, Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae, but otherwise has a spectrum of activity similar to that of other recent cephalosporins. In a clinical trial, ceftobiprole was non-inferior to vancomycin for the treatment of MRSA-associated complicated skin and skin structure infections (cSSSIs). Doripenem, a new carbapenem, has some activity against MRSA, but otherwise has an anti-Gram-positive spectrum of activity similar to that of imipenem and an anti-Gram-negative spectrum similar to that of meropenem. In a clinical trial, it was non-inferior to meropenem for the treatment of complicated intra-abdominal infections. Iclaprim is a dihydrofolate reductase inhibitor with greatly enhanced activity, as compared with trimethoprim, against a range of Gram-positive and Gram-negative pathogens. The limited literature concerning this agent has concentrated on its potential role in the treatment of infections with Gram-positive bacteria. A clinical trial has demonstrated the non-inferiority of iclaprim, as compared with linezolid, in the treatment of cSSSIs, including those associated with MRSA.
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Department of Infection, King's College and Guy's and St Thomas Hospital, London, UK. gary.french@kcl.ac.uk
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use*; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D012106:Research / Q000639:trends*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D011743:Pyrimidines; C486448:iclaprim; C443755:ceftobiprole; D000077726:Doripenem