February 2011

News read or heard lately

Honing P. aeruginosa therapy

A study conducted by clinical pharmacists at the University of Pittsburgh Medical Center led to revised antibiotic treatment recommendations for patients with infections caused by Pseudomonas aeruginosa, according to a report in the December 2011 “Pharmacy Practice News.”

The pharmacist-researchers devised a combination antibiogram that applied pharmacodynamic breakpoints to minimum inhibitory concentration (MIC) distributions for a range of commonly used antibiotics. The inclusion of pharmacodynamic breakpoints led to substantial changes in antibiotic treatment recommendations, say the researchers, who presented their results at the American College of Clinical Pharmacy annual meeting in October 2011.

Brian A. Potoski, PharmD, BCPS (AQ-ID), associate director of UPMC’s antibiotic management program and one of the study’s authors, described as one of the “striking” findings that cefepime—an antibiotic UPMC has used extensively as monotherapy—probably should not be used in the empiric setting, “at least by itself, based on the PD breakpoint.”

Drawing on UPMC’s susceptibility and MIC data, the researchers found that the optimal pharmacodynamic-based combination therapy for P. aeruginosa involved using a β-lactam antibiotic with an aminoglycoside. Piperacillin-tazobactam plus tobramycin was the top selection reported in the study, with meropenem plus tobramycin a close second. The study was based on 376 P. aeruginosa isolates identified from blood or bronchoalveolar lavage cultures at three ICUs from January 2009 to December 2010.

The pharmacodynamic breakpoints that the researchers recommended were at least 50 percent lower than those published by the Clinical and Laboratory Standards Institute. The breakpoints recommended in the Pittsburgh P. aeruginosa antibiogram included cefepime no greater than 4 mcg/mL (versus the CLSI standard of up to 8 mcg/mL), piperacillin-tazobactam no greater than 16 mcg/mL (versus up to 64 mcg/mL), meropenem 2 mcg/mL or less (versus 4 mcg/mL), and tobramycin 2 mcg/mL or less (versus up to 4 mcg/mL).

Biomarker data released for Alzheimer’s disease

The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium has released biomarker data from studies intended to improve the ability to diagnose and measure the progression of Alz-heimer’s disease. The consortium is a public-private partnership that seeks to develop biomarkers to expedite the diagnosis and treatment of major diseases.

Researchers used proteomics to identify biomarkers for Alzheimer’s disease using cerebrospinal fluid samples provided by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the largest public-private partnership to date in AD research. These data are now available to the global research community (adni.loni.ucla.edu).

The Biomarkers Consortium study, “Use of targeted multiplex proteomic strategies to identify CSF-based biomarkers in Alzheimer’s disease,” is the second part of a two-phased effort using samples collected by ADNI to qualify biomarker panels in plasma and CSF to diagnose and monitor disease progression in people with AD. The study was conducted by a team of researchers from academia, pharmaceutical companies, the NIH, and the FDA under the auspices of the FNIH Biomarkers Consortium. Additional studies using ADNI CSF samples are underway as part of this project.

“This set of data realizes a 15-year-old vision of having a public domain database allowing interrogation of the relationship between a range of physiologically important proteins in blood and cerebrospinal fluid and genetic variation,” said William Potter, PhD, former vice president of translational neuroscience at Merck Research Laboratories, and advisor to the FNIH Biomarkers Consortium. “As such, it will serve not only to advance methods of AD drug development, but for any central nervous system condition of interest.”

Physicians, patients, and lab test results

Giving patients access to test results directly from the laboratory by request, as proposed Sept. 14, 2011 by the Department of HHS, the CMS, and the CDC, could improve the safety of result followup, but the potential consequences and benefits should be rigorously evaluated, say Traber Davis Giardina, MA, MSW, and Hardeep Singh, MD, MPH, in their Dec. 14, 2011 commentary, “Should patients get direct access to their laboratory test results?” (JAMA. 306:2502–2503).

Giardina and Dr. Singh, of Houston VA Health Services Research and Development Center of Excellence, Michael E. DeBakey VA Medical Center, and Department of Medicine, Section of Health Services Research, Baylor College of Medicine, consider the potential effects of the proposed approach from both patient and clinician perspectives. Pointing out that the proposal doesn’t offer guidance to labs on releasing highly sensitive results or provide physicians the opportunity to receive the result before the patient, they say physicians have expressed concern about the anxiety or confusion that could result in the absence of the type of explanation a physician provides.

How patients would respond to abnormalities that are not clinically significant and what effect this would have on physician workload and potential for reimbursement remain to be seen, the authors write.

Though direct notification of results might help patients make decisions about their care, data to support the idea are lacking, they say. And “it is unknown what effect dual patient-clinician notification might have on follow-up rates if physicians more explicitly share the ownership of patients’ test results and shift responsibility for initiating follow-up care to patients.” As an example, they cite a 2009 Archives of Internal Medicine study that found worse followup when both the primary care practitioners and the ordering clinician were notified of an abnormal imaging result—because of the lack of clarity about who is responsible for followup.

The authors say the proposal will affect 39 states and territories in which no current laws regulate direct result delivery to patients, or where state law bans the practice.

In comments submitted Nov. 14, 2011, the CAP said it supports the release of lab test results to patients upon request but with these five changes so that the final rule:

• Ensures that test results are not released to the patient in advance of release to the ordering clinician except in emergency situations.
• Requires that the ordering physician disclose to the patient the identity of the testing laboratory.
• Requires that labs be informed of the identity of the responsible physician.
• Preempts and voids any state restriction impeding lab-initiated release of results and/or lab-initiated contact with patients.
• Does not require the lab to observe a defined time lag between delivery of results to the ordering clinician (to provide the physician time to inform the patient) and release of results in response to a patient request.

The CAP recommends that HHS not finalize the Sept. 14 proposal until after the HIPAA changes in a 2010 proposal that implements the privacy and security provisions of the HITECH Act are also made final.

Nanosphere staph test cleared

Nanosphere has received FDA 510(k) clearance for its Verigene Staphylococcus blood culture nucleic acid test (BC-S).

The automated test detects Staphylococcus aureus, Staphylococcus epidermidis, and the mecA gene and provides species and resistance results from two types of gram-positive blood culture bottles within 2.5 hours.

The Verigene BC-S test was submitted to the FDA as the first phase of a stepwise process to obtain clearance for a larger test panel, which will be marketed as the Verigene BC-GP test. The BC-GP test will consist of up to 16 bacterial/resistance marker targets, all on a single test cartridge. A second 510(k), necessary to obtain clearance for the full BC-GP test panel, is under FDA review.

Nanosphere has obtained the CE-IVD mark for regulatory approval in Europe of the full BC-GP test.

Affymetrix acquires eBioscience

Affymetrix has signed a definitive agreement to acquire eBioscience, a company that offers flow cytometry and immunoassay reagents for immunology and oncology research and diagnostics. Under the terms of the deal, Affymetrix will acquire eBioscience for $330 million.

“eBioscience complements our traditional businesses of genomics and cytogenetics, and dramatically strengthens our foundation in molecular diagnostics,” said Stephen P. A. Fodor, PhD, founder and chairman of Affymetrix.

Affymetrix, headquartered in Santa Clara, Calif., expects to maintain eBioscience’s management team and operations in San Diego.