Rapid Molecular Testing Saves Hospitals Time, Money Ruling Out TB

Molecular testing facilitates faster discontinuation of respiratory isolation for individuals undergoing evaluation for active tuberculosis (TB) in U.S. hospitals, according to a study published Aug. 27 in JAMA Internal Medicine. Incorporation of sputum molecular testing is not only safe and feasible in real-world clinical care, but it yields substantial patient, clinical, and economic benefits.

"These measures of impact place rapid molecular testing for TB among a select group of interventions that have been shown to advance the 'quadruple aim': improved population health, a better patient experience, a better clinician experience, and lower costs," write the authors led by Lelia Chaisson, from Johns Hopkins University in Baltimore, Md.

Infection control measures are intended to prevent in-hospital transmission of TB, but can lead to prolonged stays in isolation rooms due to the time it takes to run conventional rapid diagnostic testing for TB, with serial sputum collection for microscopic examination taking two or more days. Despite this considerable burden on patients, clinicians, and hospitals, and national recommendations, molecular testing has not been widely adopted as a replacement to sputum-smear microscopy to guide discontinuation of respiratory isolation.

The current study evaluated implementation of rapid, molecular testing at Zuckerberg San Francisco General Hospital and Trauma Center. Prior to the 2015 introduction of molecular testing, the hospitals TB infection-control policies required all possible TB patients to stay in isolation for collection of two or more sputa over two separate days for concentrated acid-fast bacilli smear microscopy and mycobacterial culture. Testing was carried out in a single batch once daily. Patients with a high clinical probability of TB were placed in airborne infection isolation, while patients at low clinical probability of TB could be placed in respiratory isolation in conventional private rooms without negative-pressure ventilation systems, if no airborne infection isolation rooms were available. Isolation could be discontinued for TB-negative patients when two or more sputa tested negative.

The 2015 update for discontinuing respiratory isolation incorporated molecular testing. The updated algorithm allowed discontinuation of isolation after negative smear and/or molecular assay examination results of two sputa for patients with low probability of infection or for three negative sputa results for patients with a high probability of infection, based on clinical presentation.

From January 2014 to January 2016, which includes before and after implementation, 621 underwent sputum examination for evaluation for active pulmonary TB. Molecular sputum testing was conducted using GeneXpert MTB/RIF (Cepheid; Sunnyvale, Calif.), which provides testing results in less than two hours.

The researchers found that the median time from hospital admission until initial sputum collection was similar pre- and post-implementation (19.1 versus 18.0 hours, respectively).  Clinicians completed the TB testing evaluation process at similar rates pre- and post-implementation (77 versus 81 percent, respectively).

Among the 320 patients evaluated in the post-implementation period, clinicians ordered molecular testing 73 percent of patients and received results for 98 percent of tests ordered.  For patients with assay testing ordered, 74 percent had one test ordered, 24 percent had two tests ordered, and 3 percent had three tests ordered (totaling 302 molecular tests ordered).

Ten patients pre-implementation (4.3 percent) and nine patients post- implementation (2.7 percent) after had positive rapid TB test results, including six assay-positive and eight smear-positive results after implementation. The molecular testing algorithm accurately diagnosed all seven patients with culture-confirmed TB and excluded TB in all 251 patients with culture-negative results, yielding one false-negative assay result, which was safely diagnosed based on an additional sputum sample sent for molecular testing, per the risk-stratified algorithm. The algorithm also detected one patient with TB who had a negative smear evaluation, who would have otherwise gone undetected.

Post-implementation, median time to first test result after sputum collection significantly decreased from 18.4 hours to 4.6 hours, as did median time to final test result after sputum collection (a decrease from 39.1 hours to 22.4 hours). Mean time in isolation for patients with negative test results significantly decreased 29 percent (from 3.9 days per patient pre-implementation to 2.8 days post-implementation. Similarly, median hospital length of stay decreased (6.0 to 4.9 days) and mean hospital costs per patient with negative rapid TB test results decreased from $46,921 to $33,574 post-implementation, yielding an average savings of $13,347 per patient.

"The diffusion into clinical and public health microbiology laboratories has been slow owing to budget constraints in the laboratories, physicians wary to act on molecular results, and general reluctance to implement change for such

a new technology," writes Max Salfinger, M.D., from National Jewish Health in Denver, Co.,  in an accompanying editorial. "The evidence showed that clinicians and infection preventionists, as well as hospital administrators should work with all stakeholders to identify barriers at their institution (e.g., outdated electronic ordering algorithms, not acknowledging system-wide savings when only focused on laboratory expense) preventing a wider implementation of nucleic acid amplification test testing.

Takeaway: A molecular testing strategy to rule out active TB infection in the hospital setting is feasible; reduces turnaround time for testing, isolation, and hospital length of stay; and substantially cuts hospital costs, compared to a conventional microscopy-based testing strategy.