WASHINGTON, D.C. - With bacteremia that is unresponsive to treatment becoming more persistent and dangerous, representatives of eight pharmaceutical companies pleaded with the Food and Drug Administration (FDA) to classify it as a disease instead of just a marker for severe underlying infection.
Defining bacteremia as a primary infection - as it was years ago - would make it possible to develop antibiotics to treat it directly, industry representatives stated at a recent FDA/industry conference here.
"Three major changes in nosocomial bacteremia over the last decade support making it an approvable clinical indication," said Francis P. Tally, MD, from Cubist Pharmaceuticals Inc. "A significant number of gram-positive bacteremia patients have no identifiable underlying infection," he said. "Yet some reports have noted a 30% in-hospital mortality that can't be attributed to anything but bacteremia."
Tally argued that physicians trying to manage patients with severe primary bacteremias need a real change in the official view that only a source-specific bacteremia is an indication for drug approval.
"Recent studies show that some 25% of resistant Staphylococcus aureus infections and 47% of VRE have no identifiable source. That means there's no approved drug available to help these patients."
He cautioned against restricting industry from developing approvable products. This creates an ever-increasing patient population without therapeutic options, according to Tally and other industry speakers.
"The absence of a bacteremia indication for many recently approved anti-infective drug products leaves clinicians without sufficient guidance for treating these seriously ill patients," said Michael Zeckel, MD, from Lilly Research Laboratories. "Without such guidance, a physician may use an antimicrobial agent with only limited potential efficacy against a highly lethal infection."
Zeckel also suggested that "Even knowledge that an antibiotic is approved for a relevant primary indication [i.e. nosocomial pneumonia including cases complicated by bacteremia] may not help the clinician, since a positive blood culture may be the first evidence of infection in 50% of bacteremic patients; a substantial proportion [22% to 48%] of bacteremic patients have no primary site of infection identified even in retrospect; patients may have multiple sites of infection, colonization and metastatic involvement, making specific identification of the primary site of infection uncertain; and identification of the primary site of infection, even in patients with bacteremia, may not be accurate."
Zeckel concluded, "Bacteremia should be considered as an appropriate indication for regulatory approval given: the importance of bacteremia as a public health problem; the ability to explicitly define the syndrome; the relative specificity of blood cultures in identifying the etiologic agent; the clarity of endpoints; and the need for guidance for clinicians charged with selecting appropriate antibiotic therapy for a common and potentially serious infection."
Considering bacteremia as an approvable indication, industry speakers urged that patients be enrolled sooner in clinical trials and notas was the case with quinupristin/dalfopristin (Synercid, Rhone-Poulenc Rorer), which awaits approvalhave entry criteria restricted to treatment failure.
Other recommended changes in clinical trial design for bacteremia included fewer blood cultures than currently required and the use of adjunctive therapy.
The FDA's Anti-Infective Drug Products Advisory Committee will discuss these and many other suggestions when it meets later this month to encourage new drug development to fight antibiotic resistance.
Other drug companies represented at the conference included Bristol Myers Squibb, Pharmacia & Upjohn, Schering-Plough, SmithKline Beecham and MRL Pharmaceutical Services.
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