Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections.
Antibiotic resistance is an ever-increasing concern in the treatment of severe skin and skin-structure infections, pneumonia, bacteremia and other serious infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus, group A Streptococcus and vancomycin-resistant Enterococcus. In this review, we summarize the current status of both US FDA-approved and investigational agents aimed at this group of pathogens. We also describe, in detail, the chemistry, mechanism of action, pharmacokinetic properties and spectrum of microbiological activity of iclaprim, a novel dihydrofolate reductase inhibitor recently awarded fast-track approval status by the FDA. Finally, we review the clinical efficacy of iclaprim compared with linezolid for skin and skin-structure infections as demonstrated in Phase III randomized, controlled trials, and comment on its potential role in the treatment of other severe infections with drug-resistant Gram-positive pathogens.
Morgan
Andrew
A
Veterans Affairs Medical Center, Boise, Idaho, USA and, Idaho State University School of Pharmacy, Pocatello, Idaho 83702, USA.
Cofer
Christine
C
Stevens
Dennis L
DL
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D011743:Pyrimidines; C486448:iclaprim