Pyrazinamide Resistance, Mycobacterium tuberculosis Lineage and Treatment Outcomes in San Francisco, California

Abstract

BackgroundPyrazinamide (PZA) is a first line agent for the treatment of active tuberculosis. PZA is also considered a potent companion drug for newer regimens under development. There are limited data on the demographic, clinical, and pathogen characteristics of PZA resistant tuberculosis.MethodsUsing a retrospective cohort study design, we evaluated all PZA resistant M. tuberculosis (M.tb) and M. bovis cases reported in San Francisco from 1991 to 2011. Demographic, clinical, and molecular data were analyzed. M.tb lineage was determined for all PZA resistant strains and compared to PZA susceptible strains.ResultsPZA resistance was identified in 1.8% (50 of 2,842) of mycobacterial isolates tested, corresponding to a case rate of 0.3 per 100,000 in the population. Monoresistant PZA infection was associated with the Hispanic population ([OR], 6.3; 95% [CI], 1.97–20.16) and 48% of cases were due to M. bovis. Infection with monoresistant PZA was also associated with extrapulmonary disease ([OR], 6.0; 95% [CI], 2.70–13.26). There was no statistically significant difference between treatment failure and mortality rates in patients infected with PZA monoresistance compared to pansusceptible controls (4% vs. 8%, p = 0.51), or those with PZA and MDR resistance (PZA-MDR) compared to MDR controls (18% vs. 29%, p = 0.40). PZA resistance was not associated with M.tb lineage.ConclusionsAcross two decades of comprehensive epidemiologic data on tuberculosis in San Francisco County, PZA resistance was uncommon. PZA resistance caused predominantly extrapulmonary disease and was more common in Hispanics compared to other ethnicities, with nearly half the cases attributed to M. bovis. No association was found between PZA monoresistance and M.tb lineage. Treatment outcomes were not adversely influenced by the presence of PZA resistance.

Pyrazinamide Susceptibility and pncA Mutation Profiles of Mycobacterium tuberculosis among Multidrug-Resistant Tuberculosis Patients in Bangladesh

“…Except for three cases (two of which were caused by PZA r isolates), all smear and culture conversions occurred within 6 months of treatment. These data reveal that the treatment outcome may not be heavily influenced by the PZA susceptibility status, which has also been described by earlier researchers ( 37 ).…”

“…Due to an insufficient sample size, we were unable to conclude that PZA susceptibility does not significantly associate with the genetic type of the M. tuberculosis isolates. However, a study from California also showed that PZA susceptibility does not correlate with the genetic lineage of M. tuberculosis ( 37 ).…”

The Influence of Pyrazinamide Monoresistance on Treatment Outcomes in Tuberculosis Patients from Southern China

“…No significant difference (P > 0.05) was observed between the PZA-monoresistant and PZAsensitive patients in total and partial lesion elimination rates after the intensive phase ( Table 3). This is consistent with our previous study [23] and a recent report in San Francisco, California [24]. Liang et al reported that the multiple drug resistance, but not the single drug-resistance, could alter the sputum conversion after 2 months treatment [25].…”

Novel potential diagnostic test for Mycobacterium tuberculosis complex using combined immunomagnetic separation (IMS) and PCR-CTPP

“…; Budzik et al . ). Multiplex PCR targeting to the RD1 gene has been validated for dual detection of MTC and Myco.…”

“…In addition, the naturally pyrazinamide (PZA) resistant Myco. bovis (Konno et al 1967) and PZA-monoresistant M. tuberculosis should be considerably identified (Kurbatova et al 2013;Budzik et al 2014). Multiplex PCR targeting to the RD1 gene has been validated for dual detection of MTC and Myco.…”