Annals of Long Term Care

The American Thoracic Society’s (ATS) Annual International Conference featured a special update session on the Influenza A (H1N1) pandemic. Ironically, several thousand of the anticipated 15,000-16,000 attendees cancelled travel plans to attend the conference because of their governments’ recommendations against travel to the United States. The conference is one of the largest gatherings of researchers, clinicians, and healthcare workers in the field of respiratory medicine and has been a preferred venue for the presentation of breakthrough scientific developments in that area. The entire program listings and abstracts are available on the ATS journal website: http://ajrccm.atsjournals.org/content/vol179/1_MeetingAbstracts/ (free to ATS members and pay per view for nonmembers).

“A Silver Bullet”

One of the most exciting developments in the management of bacterial respiratory infections is the new class of antimicrobials called silver carbene complexes (SCCs). SCCs have already been shown to be effective in the treatment of resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumonia, which are common in institutionalized patients. The SCCs are encapsulated into L-tyrosine polyphosphate nanoparticles to achieve a timed-release effect. Thus, dosing of the SCCs is only once per day, and the nanoparticles retain antimicrobial activity over 3 days. The particles are less than a micron in size and can be delivered easily to the alveoli using small-droplet nebulization. To date, the SCCs have shown antimicrobial effectiveness against all bacteria that have been tested, including MRSA, Klebsiella, Pseudomonas, Bacillus anthracis (anthrax), and Yersinia pestis (plague), and they are currently being tested against extremely drug-resistant mycobacterium tuberculosis.

The SCCs’ mechanism of action is inference with a bacteria’s copper-dependent enzyme systems (intracellular energy production) and DNA replication. The design of the delivery molecule is intended to make it compatible with water solutions so it can be given by nebulization for lung infections, but is also compatible with intravenous administration. In vivo animal testing and limited human clinical trials have found no adverse effects. The patent owner of SCCs states that it can easily be produced commercially in large quantities, and that the production process is not expensive, so ultimate retail cost should not be high. The obvious additional use of SCCs beyond healthcare applications is for defense against and treatment of bacterial agents used as biological or terrorist weapons. Its demonstrated safety and broad applications should help hasten support for completion of necessary clinical trials and approval by the Food and Drug Administration.

“Search and Destroy”

Researchers from the University College London reported preliminary success with a novel cancer chemotherapy employing adult mesenchymal stem cells (MSCs). These MSCs are autologous adult stem cells that can be readily harvested from a patient’s bone marrow. The MSCs are then engineered to carry a protein (tumor necrosis factor-alpha [TNF-alpha]) that will induce an apoptotic cascade in a target cell when activated. The MSC is also armed with a tetracycline promoter trigger, so it will only activate apoptosis in the presence of the promoter. Researchers have found that MSCs are naturally attracted to or can “home in on” cancer cells because of the chemokines that are produced by most cancer cells. The observation of this unique attraction led to the inspiration that they could use this homing trait of MSCs to selectively deliver tumoricidal agents to cancer cells. TNF is an ideal agent because it induces cell death in the target cell with no collateral damage to adjacent healthy tissues.