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Pyrosequencing improves time to MDR-TB diagnosis, treatment

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November 8, 2018

The use of pyrosequencing to detect mutations associated with resistance to certain antibiotics resulted in patients with multidrug-resistant tuberculosis receiving effective treatment more than 5 weeks earlier than patients whose specimens were not submitted for pyrosequencing, according to study findings published in Clinical Infectious Diseases.

“By providing sequence results, pyrosequencing goes a step further than the previous molecular beacon test which only indicated whether or not a mutation was present,” Phil Lowenthal, MPH, an epidemiologist in the Tuberculosis Control Branch at the California Department of Public Health, and colleagues wrote. “Knowing the precise sequence of a mutation is critical because not all mutations confer drug resistance, and mutations that do can confer different levels of resistance.”

According to Lowenthal and colleagues, the California Department of Public Health has been using rapid molecular drug susceptibility testing with pyrosequencing since 2012 to detect mutations in Mycobacterium tuberculosis associated with resistance to isoniazid, rifampin, quinolones and injectable drugs. Resistance to first-line medication threatens control of TB and is a barrier to eliminating the disease.

To determine the impact that pyrosequencing has on the clinical management of TB, Lowenthal and colleagues tracked changes made to patients’ treatment regimens after a clinician received the pyrosequencing results to determine how they influence clinical decision-making, according to the study. This information was collected via a survey of TB programs that submitted patients’ specimens for pyrosequencing conducted between Aug. 1, 2012, and July 31, 2013. They also evaluated what impact pyrosequencing had on time to effective treatment initiation.

Lowenthal and colleagues compared MDR-TB treatment initiation among patients with and without pyrosequencing testing between Aug. 1, 2012, and Dec. 31, 2016.

Among the 1,957 specimens tested using pyrosequencing, 52% were sediments, submitted a median of 8 days after collection; and 46% were culture isolates, submitted a median of 35 days after collection, Lowenthal and colleagues reported. According to the study findings, there was a median of 12 days from specimen collection to initiation of MDR-TB treatment among the 36 patients with MDR-TB and a sediment specimen that was submitted for pyrosequencing. Comparatively, when pyrosequencing was not used, initiation of MDR-TB treatment from the time of specimen collection took a median of 51 days.

According to the study, 303 patients had a completed survey. Of the clinicians providing their care, 42% (n = 126) reported changing treatment because of the pyrosequencing results. Twenty-one patients had an MDR-TB risk factor and a smear-positive sputum specimen, nine patients had pyrosequencing performed on a culture isolate and 12 patients were not diagnosed by pyrosequencing. According to the study, these patients, if the appropriate specimens were tested by pyrosequencing, would have had an opportunity for an earlier MDR-TB diagnosis.

“Further improvement can be made to reduce the time to initiate MDR-TB treatment by recognizing MDR-TB risks and submitting smear-negative sputa rapidly for pyrosequencing,” Lowenthal and colleagues wrote. – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

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