Volume 95, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, , is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, = 0.003); multidrug-resistant TB (OR = 0.349, < 0.001); and PZA-resistant TB (OR = 0.076, < 0.001). In conclusion, mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Bangsberg DR, Crowley K, Moss A, Dobkin JF, McGregor C, Neu HC, , 1997. Reduction in tuberculin skin-test conversions among medical house staff associated with improved tuberculosis infection control practices. Infect Control Hosp Epidemiol 18: 566570.[Crossref] [Google Scholar]
  2. Stricof RL, DiFerdinando GT, Jr Osten WM, Novick LF, , 1998. Tuberculosis control in New York City hospitals. Am J Infect Control 26: 270276.[Crossref] [Google Scholar]
  3. Hannan MM, Azadian BS, Gazzard BG, Hawkins DA, Hoffman PN, , 2000. Hospital infection control in an era of HIV infection and multi-drug resistant tuberculosis. J Hosp Infect 44: 511.[Crossref] [Google Scholar]
  4. Wells CD, Cegielski JP, Nelson LJ, Laserson KF, Holtz TH, Finlay A, Castro KG, Weyer K, , 2007. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis 196: S86S107.[Crossref] [Google Scholar]
  5. Kawai V, Soto G, Gilman RH, Bautista CT, Caviedes L, Huaroto L, Ticona E, Ortiz J, Tovar M, Chavez V, Rodriguez R, Escombe AR, Evans CA, , 2006. Tuberculosis mortality, drug resistance, and infectiousness in patients with and without HIV infection in Peru. Am J Trop Med Hyg 75: 10271033. [Google Scholar]
  6. Raviglione MC, Dye C, Schmidt S, Kochi A, , 1997. Assessment of worldwide tuberculosis control. WHO Global Surveillance and Monitoring Project. Lancet 350: 624629.[Crossref] [Google Scholar]
  7. Willingham FF, Schmitz TL, Contreras M, Kalangi SE, Vivar AM, Caviedes L, Schiantarelli E, Neumann PM, Bern C, Gilman RH, , 2001. Hospital control and multidrug-resistant pulmonary tuberculosis in female patients, Lima, Peru. Emerg Infect Dis 7: 123127.[Crossref] [Google Scholar]
  8. World Health Organization, 2013. Global Tuberculosis Report 2013. Geneva, Switzerland: World Health Organization. [Google Scholar]
  9. Campos PE, Suarez PG, Sanchez J, Zavala D, Arevalo J, Ticona E, Nolan CM, Hooton TM, Holmes KK, , 2003. Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru. Emerg Infect Dis 9: 15711578.[Crossref] [Google Scholar]
  10. Hu Y, Coates AR, Mitchison DA, , 2006. Sterilising action of pyrazinamide in models of dormant and rifampicin-tolerant Mycobacterium tuberculosis . Int J Tuberc Lung Dis 10: 317322. [Google Scholar]
  11. Mitchison DA, , 1985. The action of antituberculosis drugs in short-course chemotherapy. Tubercle 66: 219225.[Crossref] [Google Scholar]
  12. Steele MA, , 1988. The role of pyrazinamide in tuberculosis chemotherapy. CHEST Journal 94: 845.[Crossref] [Google Scholar]
  13. Scorpio A, Zhang Y, , 1996. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat Med 2: 662667.[Crossref] [Google Scholar]
  14. Sheen P, Ferrer P, Gilman RH, López-Llano J, Fuentes P, Valencia E, Zimic MJ, , 2009. Effect of pyrazinamidase activity on pyrazinamide resistance in Mycobacterium tuberculosis . Tuberculosis (Edinb) 89: 109113.[Crossref] [Google Scholar]
  15. Moore DAJ, Evans CAW, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Piñedo Y, Saravia JC, Salazar C, Oberhelman R, Hollm-Delgado M-G, LaChira D, Escombe AR, Friedland JS, , 2006. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 355: 15391550.[Crossref] [Google Scholar]
  16. Moore DAJ, Mendoza D, Gilman RH, Evans CAW, Hollm Delgado M-G, Guerra J, Caviedes L, Vargas D, Ticona E, Ortiz J, Soto G, Serpa J, , 2004. Microscopic observation drug susceptibility assay, a rapid, reliable diagnostic test for multidrug-resistant tuberculosis suitable for use in resource-poor settings. J Clin Microbiol 42: 44324437.[Crossref] [Google Scholar]
  17. Sheen P, Couvin D, Grandjean L, Zimic M, Dominguez M, Luna G, Gilman RH, Rastogi N, Moore DAJ, , 2013. Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance. PLoS One 8: e65873.[Crossref] [Google Scholar]
  18. Escombe AR, Moore DA, Gilman RH, Navincopa M, Ticona E, Mitchell B, Noakes C, Martinez C, Sheen P, Ramirez R, Quino W, Gonzalez A, Friedland JS, Evans CA, , 2009. Upper-room ultraviolet light and negative air ionization to prevent tuberculosis transmission. PLoS Med 6: e43.[Crossref] [Google Scholar]
  19. Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson RM, Gilman RH, , 1998. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate alamar blue assay. J Clin Microbiol 36: 362366. [Google Scholar]
  20. Caviedes L, Lee TS, Gilman RH, Sheen P, Spellman E, Lee EH, Berg DE, Montenegro-James S, The Tuberculosis Working Group in Peru, , 2000. Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. J Clin Microbiol 38: 12031208. [Google Scholar]
  21. Butler WR, Kilburn JO, , 1983. Susceptibility of Mycobacterium tuberculosis to pyrazinamide and its relationship to pyrazinamidase activity. Antimicrob Agents Chemother 24: 600601.[Crossref] [Google Scholar]
  22. Sheen P, Lozano K, Gilman RH, Valencia HJ, Loli S, Fuentes P, Grandjean L, Zimic M, , 2013. pncA gene expression and prediction factors on pyrazinamide resistance in Mycobacterium tuberculosis . Tuberculosis (Edinb) 93: 515522.[Crossref] [Google Scholar]
  23. Escombe AR, Moore DAJ, Gilman RH, Pan W, Navincopa M, Ticona E, Martínez C, Caviedes L, Sheen P, Gonzalez A, Noakes CJ, Friedland JS, Evans CA, , 2008. The infectiousness of tuberculosis patients coinfected with HIV. PLoS Med 5: e188.[Crossref] [Google Scholar]
  24. Dooley SW, , 1992. Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients. JAMA 267: 2632.[Crossref] [Google Scholar]
  25. Iwamoto T, Grandjean L, Arikawa K, Nakanishi N, Caviedes L, Coronel J, Sheen P, Wada T, Taype CA, Shaw MA, Moore DA, Gilman RH, , 2012. Genetic diversity and transmission characteristics of Beijing family strains of Mycobacterium tuberculosis in Peru. PLoS One 7: e49651.[Crossref] [Google Scholar]
  26. Huang Z, Qin C, Du J, Luo Q, Wang Y, Zhang W, Zhang X, Xiong G, Chen J, Xu X, Li W, Li J, , 2015. Evaluation of the microscopic observation drug susceptibility assay for the rapid detection of MDR-TB and XDR-TB in China: a prospective multicentre study. J Antimicrob Chemother 70: 456462.[Crossref] [Google Scholar]
  27. Evans CA, , 2011. GeneXpert: a game-changer for tuberculosis control? PLoS Med 8: e1001064.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 30 Sep 2015
  • Accepted : 24 Aug 2016
  • Published online : 07 Dec 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error