No new anti-Acinetobacter drug candidates among FDA-approved meds

A review of 1,040 FDA-approved drugs shows that “only five” — or about 0.5 percent overall — exhibit significant antibacterial activity against drug-resistant Acinetobacter baumannii, according to a report in the current issue of the Journal of Antimicrobial Chemotherapy (2010;65:2598-2601).

All five were classical antibiotic drugs. The study was an effort to identify non-antibiotic drugs that show promise against Acinetobacter — but no such candidates were identified, the authors report.

Despite that seemingly disappointing finding, however, authors from SRI International’s Center for Infectious Disease and Biodefense Research and Center for Advanced Drug Research declared the off-label “repurposing” of existing FDA-approved drugs for use against drug-resistant infections as a “viable alternative” to de novo drug discovery and development.

That assessment flatly contradicts recent ‘urgent’ calls by others for a concerted drug development effort to create new classes of medication against increasingly drug-resistant Acinetobacter strains.

Acinetobacter strains have quickly become a major source of hospital-acquired infections world-wide since the invasion of Iraq in 2003. A leading infection of soldiers and contractors wounded in Iraq, the bacteria is commonly called “Iraqibacter” in military medical circles.

The new study was the “first systematic effort” to identify already-approved drugs that could be repurposed “to tackle the growing menace of (multidrug-resistant) A. baumannii,” the authors report.

The team studied in-vitro drug effects against BAA-1605, a strain of multidrug-resistant A. baumannii originally isolated in 2006 from a Canadian combat veteran.

Even the five antibiotics identified as active against BAA-1605 — thimerosal, doxycycline HCl, Polymyxin B sulphate, rifaximin and tyrothricin — proved only weakly bactericidal.

“This extremely low hit rate supports the idea that even the (drug-susceptible) strain of A. baumannii is naturally resistant to many of the old and new classes of approved antibacterials,” the authors report.

Although fluoroquinolone drugs exhibited strong antibacterial activity against drug-susceptible A. baumannii, for example, this hopeful finding was belied by “the complete absence of fluoroquinolone activity against BAA-1605, epitomizing class resistance,” the authors report. “This extremely low number of compounds significantly active against BAA-1605 is a testament to the ability of (multidrug-resistant) A. baumannii to resist antimicrobials.”

“Our screening efforts have confirmed there are very limited options to combat A. baumannii when considering existing approved antibiotics,” the authors acknowledge in the paper’s discussion section.

Despite their daunting findings, the authors’ abstract optimistically concludes: “Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.”

SRI International is an “independent, nonprofit research and development organization,” according to the company’s website.

epiNewswire carries continuing coverage of Acinetobacter and antibiotic resistance research news.