Iclaprim comparable with vancomycin in nosocomial pneumonia
Iclaprim is as good as vancomycin in the treatment of nosocomial pneumonia, with similar cure rates and safety profile, according to the results of a phase II study.
The study included 70 patients with nosocomial pneumonia suspected or confirmed to be caused by gram-positive pathogens who were randomly assigned to three treatment arms: iclaprim 0.8 mg/kg IV q12h (iclaprim q12h; n=23), iclaprim 1.2 mg/kg IV q8h (iclaprim q8h; n=24), or vancomycin 1 g IV q12h (n=23). Treatment lasted between 7 and 14 days.
There was no significant difference in the baseline and demographic characteristics of patients across the treatment groups.
Likewise, the primary endpoint of clinical cure rate in the intention-to-treat population at test of cure (7 days post-treatment) visit was comparable: 73.9 percent in the iclaprim q12h arm, 62.5 percent in the iclaprim q8h arm and 52.2 percent in the vancomycin arm (iclaprim q12h vs vancomycin, p=0.13; iclaprim q8h vs vancomycin, p=0.47).
The respective death rates within 28 days of treatment initiation were 8.7, 12.5 and 21.7 percent for the iclaprim q12h, q8h and vancomycin arms. No statistically significant differences were noted.
All study drugs were generally well tolerated, with both iclaprim dosing regimens showing a safety profile similar to that of vancomycin.
The current data indicate that iclaprim potentially represents an important new therapeutic option for the treatment of nosocomial pneumonia, and a pivotal clinical trial is warranted to evaluate the drug’s safety and efficacy in this indication, researchers said.
Iclaprim is a novel diaminopyrimidine that inhibits bacterial dihydrofolate reductase. The drug has demonstrated potent in vitro activity against gram-positive pathogens associated with acute bacterial skin and skin structure infections and nosocomial pneumonia, including methicillin-resistant S aureus, vancomycin-intermediate S aureus, vancomycin-resistant Enterococcus species, and Streptococcus species. [Antimicrob Agents Chemother 2009;53:2171–2175; Bioorg Med Chem Lett 2003;13:4217–4221]