From the Editor

Friday, December 23, 2016 Published in On-Demand Spring 2011 Written by David Persing M.D., Ph.D., Chief Medical and Technology Officer, Cepheid

I am privileged at Cepheid to work with the some of the best minds in the diagnostics business. In this month's issue of the On-Demand newsletter, Dr. Ellen Jo Baron highlights the role of decentralized molecular testing in TB diagnostics, with a special focus on the nearly impossible challenge of diagnosing pediatric TB. This is a truly moving story which begs the question: Is there not a better solution? Cepheid is committed to developing less invasive diagnostic tools for TB in kids and in all patients with HIV where current diagnostic options are, simply put, woefully suboptimal. I am optimistic that Ellen Jo and her colleagues inside and outside the company will come up with a better way.

The Need for Better Diagnostic Tests for Pediatric Tuberculosis

Friday, December 23, 2016 Published in On-Demand Spring 2011 Written by Ellen Jo Baron, Ph.D., D(ABMM), Prof. Emerita, Stanford University Director of Medical Affairs, Cepheid

THE AERAS-CHC-CEPHEID STUDY IN CAMBODIA
Almost unfathomable to contemplate is the fact that one-third of the world's population is infected with tuberculosis (TB). Each year approximately 9 million new infections occur (most people who become infected do not exhibit symptoms of disease for many years, if ever) but around 1.6 million people die of their disease; approximately one death every 9 seconds. 80% of the world's cases occur in 22 high burden countries, identified by the World Health Organization (WHO) (Figure 1). Tuberculosis can be cured, especially if drug-susceptible and drug-resistant strains are detected early and treated appropriately. A keystone of the WHO's global plan to stop TB ("Stop TB Partnership"; http://www.stoptb.org/global/plan/) involves using smear microscopy to identify patients and to treat those patients with a course of antibiotics, with the patient being observed taking his/her drugs by a healthcare worker for at least the first two months. This "directly observed therapy short-course" (DOTS) regimen includes the oral drugs rifampin, isoniazid (INH), pyrazinamide, and ethambutol for 2 months, followed by 4 more months of INH and rifampin alone; and for patients with susceptible strains, >95% are cured. If the organism is known to be susceptible to rifampin and INH through drug susceptibility testing (DST) performed on organisms isolated in pure culture, then ethambutol may be removed from the regimen. An expanding group of patients infected with multi-drug resistant TB (MDR-TB; i.e., strains resistant to multiple drugs including both INH and rifampin) require longer therapy with more antimicrobial agents, typically fluoroquinolones, aminoglycosides, p-aminosalicylic acid, ethionamide, and others, some of which must be injected. The sooner a patient harboring a resistant strain begins taking the drugs that will actually work, the greater the likelihood that the patient will be cured, even though the therapy must continue for a much longer time than if the strain were susceptible.

Clostridium difficile Ribotype 027: Why Should We Care?

Friday, December 23, 2016 Published in On-Demand Spring 2011 Written by Ellen Jo Baron, Ph.D., D(ABMM), Prof. Emerita, Stanford University Director of Medical Affairs, Cepheid

The first hint that something new was happening with regard to Clostridum difficile infections (CDI) was a study presented at the 2004 annual meeting of the Infectious Diseases Society of America by epidemiologists from the Centers for Disease Control and Prevention (CDC) and other investigators describing an emerging epidemic strain that was typically resistant to fluoroquinolones.1

Wake-Up Call: Proficiency Testing for Today's Technology

Friday, December 23, 2016 Published in On-Demand Spring 2011 Written by Ellen Jo Baron, Ph.D., D(ABMM), Prof. Emerita, Stanford University Director of Medical Affairs, Cepheid

How Cepheid's GBS Assay Stimulated New Awareness and How Your Laboratory Should Respond to Avoid Similar Problems
Last year, a number of Cepheid's Xpert® GBS assay users "failed" some of the College of American Pathologists' group B streptococcal proficiency testing (P.T.) samples distributed in shipment D8. The users reported "positive for group B Streptococcus (GBS)" when the CAP had intended those samples to be negative and the provider of the samples had certified that they did not contain GBS. Laboratories using other nucleic acid amplification methods, such as BD GeneOhm, and those using the Cepheid SmartCycler® GBS product did not experience any positive results, and CAP's initial assessment was that the Xpert GBS assay was producing false positive results. CAP initially suspected that there was a cross-reaction with other organisms present in the challenge specimens. Although the early discussions focused on whether CAP should notify the FDA about the faulty performance of the assay, a conference call with several representatives from Cepheid and CAP resulted in an agreement to investigate the situation further. CAP's decision may have been influenced partially by a letter received from one participating laboratory documenting that the laboratory had recovered viable GBS from at least one of the supposedly negative P.T. samples after extended broth incubation.