Increasing prevalence of pyrazinamide-resistant tuberculosis

"Physicians should know that certain socio-demographic and clinical factors, as well as some mycobacterial characteristics, are associated with higher likelihood of pyrazinamide resistance," Dr. Ekaterina V. Kurbatova from CDC's Division of TB Elimination, Atlanta, Georgia, told Reuters Health by email.

"Although pyrazinamide resistance represents only a small proportion of tuberculosis cases in the U.S., the trend is increasing. This indicates that physicians should pay attention, as it may become a bigger concern in the future," she added.

Pyrazinamide plays an important role in first-line and second-line treatment of drug-susceptible and multidrug-resistant tuberculosis, but testing for pyrazinamide resistance is difficult and not always performed.

Dr. Kurbatova and colleagues analyzed the prevalence, trends, and risk factors for initial resistance to pyrazinamide among MTBC cases in the U.S. between 1999 and 2009.

Among 79,321 cases with drug susceptibility testing results, 2,167 (2.7%) had initial resistance to pyrazinamide, according to the July 9 Clinical Infectious Diseases online report.

More than a third of multidrug-resistant cases (38.0%) were resistant to pyrazinamide, compared with 2.2% of non-multidrug-resistant cases.

The increased prevalence of pyrazinamide resistance from 2.0% in 1999 to 3.3% in 2009 reflected a doubling in pyrazinamide monoresistance from 1.2% in 1999 to 2.5% in 2009.

In multivariable analysis, pyrazinamide monoresistance was associated with younger age (0-24 years), Hispanic ethnicity, HIV infection, extrapulmonary disease, and normal chest radiograph and inversely associated with Asian and Black race, substance use, homelessness, and residence in a correctional facility.

Pyrazinamide polyresistance was associated with Hispanic ethnicity, Asian race, previous TB diagnosis, and normal chest x-ray and inversely associated with age 45 years and older, whereas pyrazinamide resistance in multidrug-resistant cases was associated with female sex and previous TB diagnosis.

Half the cases of pyrazinamide resistance overall occurred with M. bovis infection.

Bacterial lineage (especially Indo-Oceanic lineage, primarily localized to South and Southeast Asia) was the primary predictor of pyrazinamide resistance among M. tuberculosis cases, rather than host characteristics.

"Pyrazinamide is a part of the standard anti-tuberculosis first-line regimen called RIPE, which stands for rifampin, isoniazid, pyrazinamide and ethambutol," Dr. Kurbatova explained. "Pyrazinamide plays a unique role in the regimen by killing semi-dormant (i.e., not actively replicating) TB bacilli not easily killed by other antibiotics. Resistance to pyrazinamide requires altering patient management and extending the length of anti-TB treatment."

"Growth-based methods of drug susceptibility testing are slow and can take 2-3 weeks," Dr. Kurbatova said. "However, if a physician suspects drug resistance, the specimen can be referred for rapid molecular detection of mutations associated with drug resistance, including resistance to pyrazinamide. The results could be available in two days after submission of the specimen. CDC offers this service free of charge."

"Since pyrazinamide is and will remain an essential part of tuberculosis treatment in the near future, our study highlights need for development of faster and more reliable methods of testing for susceptibility to pyrazinamide, so physicians can have these results when initiating treatment for tuberculosis," Dr. Kurbatova concluded.

SOURCE: http://bit.ly/1555vQ1

Clin Infect Dis 2013.

Source: Medscape Today