Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections.

Abstract

Iclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin for S. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused by S. aureus, including MRSA.

• Authors: D Krievins, R Brandt, S Hawser, P Hadvary, K Islam
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 7 Pg. 2834-40 (Jul 2009) ISSN: 1098-6596 [Electronic] United States
• PMID: 19414572 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Pyrimidines
• iclaprim
• Vancomycin

Topics

• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (administration & dosage, pharmacology, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Infusions, Intravenous
• Male
• Methicillin-Resistant Staphylococcus aureus (drug effects, pathogenicity)
• Microbial Sensitivity Tests
• Middle Aged
• Pyrimidines (administration & dosage, pharmacology, therapeutic use)
• Skin Diseases, Infectious (drug therapy, microbiology)
• Staphylococcus aureus (drug effects, pathogenicity)
• Vancomycin (administration & dosage, therapeutic use)
• Young Adult