Background Pyrazinamide (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. Methods Using 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. Results PZA 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. Conclusions Across 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.
References
[1]
Kurbatova EV, Cavanaugh JS, Dalton T, Click ES, Cegielski JP (2013) Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999–2009. Clin Infect Dis 57: 1081–1093. doi: 10.1093/cid/cit452
[2]
Stoffels K, Mathys V, Fauville-Dufaux M, Wintjens R, Bifani P (2012) Systematic analysis of pyrazinamide-resistant spontaneous mutants and clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 56: 5186–5193. doi: 10.1128/aac.05385-11
[3]
Yee DP, Menzies D, Brassard P (2012) Clinical outcomes of pyrazinamide-monoresistant Mycobacterium tuberculosis in Quebec. Int J Tuberc Lung Dis 16: 604–609. doi: 10.5588/ijtld.11.0376
[4]
Conde MB, Lapa E SilvaJR (2011) New regimens for reducing the duration of the treatment of drug-susceptible pulmonary tuberculosis. Drug Dev Res 72: 501–508. doi: 10.1002/ddr.20456
[5]
Gagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC, et al. (2006) Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103: 2869–2873. doi: 10.1073/pnas.0511240103
[6]
Firdessa R, Berg S, Hailu E, Schelling E, Gumi B, et al. (2013) Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg Infect Dis 19: 460–463. doi: 10.3201/eid1903.120256
[7]
Niemann S, Richter E, Rusch-Gerdes S (2000) Differentiation among members of the Mycobacterium tuberculosis complex by molecular and biochemical features: Evidence for two pyrazinamide-susceptible subtypes of M. bovis. J Clin Microbiol 38: 152–157.
[8]
van Embden JD, Cave MD, Crawford JT, Dale JW, Eisenach KD, et al. (1993) Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: Recommendations for a standardized methodology. J Clin Microbiol 31: 406–409.
[9]
Rhee JT, Tanaka MM, Behr MA, Agasino CB, Paz EA, et al. (2000) Use of multiple markers in population-based molecular epidemiologic studies of tuberculosis. Int J Tuberc Lung Dis 4: 1111–1119.
[10]
American Thoracic Society, CDC, Infectious Diseases Society of America (2003) Treatment of tuberculosis. MMWR Recomm Rep 52: 1–77.
[11]
Gagneux S, Burgos MV, DeRiemer K, Encisco A, Munoz S, et al. (2006) Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis. PLoS Pathog 2: e61. doi: 10.1371/journal.ppat.0020061
[12]
van Deutekom H, Hoijng SP, de Haas PE, Langendam MW, Horsman A, et al. (2004) Clustered tuberculosis cases: Do they represent recent transmission and can they be detected earlier? Am J Respir Crit Care Med 169: 806–810. doi: 10.1164/rccm.200306-856oc
[13]
Centers for Disease Control and Prevention (CDC) (2013) Reported tuberculosis in the United States, 2012.
[14]
de Jong BC, Onipede A, Pym AS, Gagneux S, Aga RS, et al. (2005) Does resistance to pyrazinamide accurately indicate the presence of Mycobacterium bovis? J Clin Microbiol 43: 3530–3532. doi: 10.1128/jcm.43.7.3530-3532.2005
[15]
Hlavsa MC, Moonan PK, Cowan LS, Navin TR, Kammerer JS, et al. (2008) Human tuberculosis due to Mycobacterium bovis in the United States, 1995–2005. Clin Infect Dis 47: 168–175. doi: 10.1086/589240
[16]
Hesseling AC, Rabie H, Marais BJ, Manders M, Lips M, et al. (2006) Bacille calmette-guerin vaccine-induced disease in HIV-infected and HIV-uninfected children. Clin Infect Dis 42: 548–558. doi: 10.1086/499953
[17]
Gonzalez OY, Musher DM, Brar I, Furgeson S, Boktour MR, et al. (2003) Spectrum of Bacille calmette-guerin (BCG) infection after intravesical BCG immunotherapy. Clin Infect Dis 36: 140–148. doi: 10.1086/344908
