NEW YORK (GenomeWeb) – A new study has shown that hospitals in the US and other low-burden tuberculosis settings can shorten the amount of time suspected TB patients need to be isolated and save thousands of dollars per patient by implementing rapid molecular testing alongside or in place of traditional smear microscopy testing.
In a paper published today in JAMA Internal Medicine, a team led by clinical researchers from the University of California, San Francisco explained that nosocomial transmission of TB remains an important public health consequence of delayed diagnosis.
The researchers noted that the US Centers for Disease Control and Prevention has developed guidelines, last updated in 2005, for risk-stratification and infection-control procedures to prevent hospital outbreaks of the disease. A major component of these guidelines is the isolation of suspected TB patients in negative-pressure ventilated rooms, which can last for several days because smear microscopy requires that sputum be collected from patients over the course of two or more days. Such isolation procedures are resource-intensive, not to mention difficult for the patient.
The UCSF team and other researchers had previously determined that rapid, automated molecular testing with Xpert MTB/RIF, a cartridge-based real-time PCR assay from Cepheid (a Danaher company), can provide results in less than two hours, and might be used to substantially decrease the duration of patient isolation.
Despite several studies demonstrating the diagnostic accuracy of this test, and endorsements by regulatory authorities and professional societies, there is next to no data on the clinical impact of tis implementation for this purpose, the UCSF researchers noted.
In their JAMA Internal Medicine study, the researchers analyzed 621 hospitalized patients whose sputum was being evaluated for active pulmonary TB from January 2014 to January 2016 at the Zuckerberg San Francisco General Hospital and Trauma Center.
The prospective study was conducted in a "before-and-after" fashion, with 301 consecutive patients first analyzed using traditional smear microscopy and culture, and the following 320 patients evaluated following the hospital-wide implementation of rapid, automated molecular testing with GeneXpert MTB/RIF, a cartridge-based real-time PCR assay from Cepheid.
Of the 301 pre-implementation patients who had at least one sputum microscopy test and culture ordered, 233, or 77 percent, underwent the study's rapid TB testing evaluation process. Of the 320 patients examined after molecular testing implementation, clinicians ordered molecular testing for 234, or 73 percent of patients, and received results for 295 of 302 tests ordered (some patients received multiple molecular tests).
The molecular testing workflow successfully diagnosed all seven patients with culture-confirmed TB and excluded the disease in 251 patients whose culture tests were negative for Mycobacterium tuberculosis. In addition, the molecular workflow detected one patient who had a negative smear test and would have otherwise gone undiagnosed.
More importantly for the purposes of the study, when comparing the molecular with the non-molecular workflow, the median time to final rapid test result was dropped to about 24 hours from 39 hours, time to discontinuation of patient isolation was reduced to 2.5 days from 2.9 days, and time to hospital discharge fell to 4.9 days from 6.0 days. On average, this translated to an average per-patient savings of $13,347.
In an editorial accompanying the paper in JAMA Internal Medicine, Max Salfinger of the department of medicine at National Jewish Health in Denver, noted that "although these differences do not seem dramatic, the savings they produce are meaningful" as the authors estimated that utilization and costs for approximately 250 patients completing TB evaluation each year would amount to a total annual savings to the hospital of $3.3 million.
"So far, molecular assays have been used to rapidly diagnose/rule in TB, especially drug-resistant TB," Salfinger wrote. "What about using a molecular assay in ruling out TB disease? … The sooner TB is ruled out using molecular assays, the sooner these patients can be released from airborne infection isolation."
Salfinger further noted that the results of the study are "very encouraging" and demonstrate that "clinicians and infection preventionists, as well as hospital administrators, should work with all stakeholders to identify barriers at their institutions … preventing a wider implementation of [nucleic acid amplification testing]. In addition, they should validate this new algorithm so their institutions can reap the potential substantial savings that result from using a NAAT for patients with possible TB in airborne infection isolation."
The UCSF researchers noted that limitations of their study included the fact that it was conducted at a single academic center where clinicians have substantial experience with TB evaluation, "potentially limiting generalizability."
Furthermore, they said that "before-and-after" studies are susceptible to false inferences if underlying trends over time are driving changes that might be attributed to the intervention. However, they said that they reduced the risk of this by comparing two 12-month periods before and after molecular testing implementation "to minimize the effects of seasonal variations in hospital census or experience among physicians in training."
In summary, the researchers noted that their data should inform revision of TB infection control guidelines from the CDC, which is urgently needed because they have not been updated since the introduction of semiautomated molecular tests such as Xpert MTB/RIF.
"Routine use of molecular assay testing should be strongly considered to provide faster, more patient-centered care to hospitalized patients undergoing evaluation for TB in the US and other low TB-burden settings, they concluded."