Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections.
OBJECTIVE
To review the pharmacology, microbiology, in vitro susceptibility, pharmacokinetics, clinical trial data, safety, and tolerability of iclaprim, a novel dihydrofolate reductase (DHFR) inhibitor.


METHODS
A MEDLINE search was conducted from 1966 through December 2008. Additional sources included abstracts from meetings of the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 2001 to 2008 and information available from the manufacturer's Web site.


METHODS
In vitro and clinical studies, in addition to Phase 1, 2, and 3 clinical trials, were included.


RESULTS
Iclaprim, a novel diaminopyrimidine and DHFR antagonist, has a mechanism of action similar to that of trimethoprim. It has in vitro activity mainly against gram-positive organisms, including resistant Staphylococcus aureus. In Phase 2 and 3 clinical trials, oral and intravenous administration of iclaprim was effective and well tolerated for the treatment of complicated skin and skin structure infections (cSSSI). Trials are currently ongoing for the treatment of ventilator-associated and healthcare-associated pneumonia.


CONCLUSIONS
Iclaprim is a promising antimicrobial agent for the treatment of gram-positive organisms, including resistant S. aureus and trimethoprim-, macrolide-, fluoroquinolone-, and glycopeptide-resistant strains. Additionally, in vitro activity similar to that of trimethoprim has been observed against gram-negative and atypical organisms.
Sincak
Carrie A
CA
College of Pharmacy, Midwestern University Chicago, Downers Grove, IL 60515, USA. csinca@midwestern.edu
Schmidt
Justin M
JM
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D024881:Drug Resistance, Bacterial; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006094:Gram-Positive Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C486448:iclaprim; D013762:Tetrahydrofolate Dehydrogenase