Advertisement

Hospital Water and Opportunities for Infection Prevention

  • Brooke K. Decker
  • Tara N. Palmore
Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Healthcare Associated Infections

Abstract

Nosocomial waterborne pathogens may reach patients through several modes of transmission. Colonization of healthcare facility waterworks can occur in the proximal infrastructure, in the distal water outlets, or both. Infections with waterborne organisms such as Legionella, mycobacteria, Pseudomonas, and others cause significant morbidity and mortality, particularly in immunocompromised patients. Hospitals should have prospective water safety plans that include preventive measures, as prevention is preferable to remediation of contaminated hospital water distribution systems. Whole-genome sequencing may provide more informative epidemiologic data to link patient infections with hospital water isolates.

Keywords

Nosocomial Waterborne Legionella 

Notes

Acknowledgments

This work was supported by the Intramural Research Program of the NIH Clinical Center.

Compliance with Ethics Guidelines

Conflict of Interest

Tara Palmore and Brooke Decker have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Conger NG, O'Connell RJ, Laurel VL, Olivier KN, Graviss EA, Williams-Bouyer N, et al. Mycobacterium simae outbreak associated with a hospital water supply. Infect Control Hosp Epidemiol. 2004;25:1050–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Williams MM, Armbruster CR, Arduino MJ. Plumbing of hospital premises is a reservoir for opportunistically pathogenic microorganisms: a review. Biofouling. 2013;29:147–62.PubMedCrossRefGoogle Scholar
  3. 3.
    Yiallouros PK, Papadouri T, Karaoli C, Papamichael E, Zeniou M, Pieridou-Bagatzouni D, et al. First outbreak of nosocomial Legionella infection in term neonates caused by a cold mist ultrasonic humidifier. Clin Infect Dis. 2013;57:48–56.PubMedCrossRefGoogle Scholar
  4. 4.
    Moran-Gilad J, Lazarovitch T, Mentasti M, Harrison T, Weinberger M, Mordish Y, et al. Humidifier-associated paediatric Legionnaires' disease, Israel, February 2012. Euro Surveill. 2012;17:20293.PubMedGoogle Scholar
  5. 5.
    Osawa K, Shigemura K, Abe Y, Jikimoto T, Yoshida H, Fujisawa M, et al. A case of nosocomial Legionella pneumonia associated with a contaminated hospital cooling tower. J Infect Chemother. 2014;20:68–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Higa F, Koide M, Haroon A, Haranaga S, Yamashiro T, Tateyama M, et al. Legionella pneumophila contamination in a steam towel warmer in a hospital setting. J Hosp Infect. 2012;80:259–61.PubMedCrossRefGoogle Scholar
  7. 7.•
    Williams MM, Chen TH, Keane T, Toney N, Toney S, Armbruster CR, et al. Point-of-use membrane filtration and hyperchlorination to prevent patient exposure to rapidly growing mycobacteria in the potable water supply of a skilled nursing facility. Infect Control Hosp Epidemiol. 2011;32:837–44. This report provides an excellent description of the investigation into contamination of a water distribution system in a healthcare facility, as well as the outcomes of remediation efforts.PubMedCrossRefGoogle Scholar
  8. 8.
    Lucero CA, Cohen AL, Trevino I, Rupp AH, Harris M, Forkan-Kelly S, et al. Outbreak of Burkholderia cepacia complex among ventilated pediatric patients linked to hospital sinks. Am J Infect Control. 2011;39:775–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Peterson AE, Chitnis AS, Xiang N, Scaletta JM, Geist R, Schwartz J, et al. Clonally related Burkholderia contaminans among ventilated patients without cystic fibrosis. Am J Infect Control. 2013;41:1298–300.PubMedCrossRefGoogle Scholar
  10. 10.
    Levy PY, Teysseire N, Etienne J, Raoult D. A nosocomial outbreak of Legionella pneumophila caused by contaminated transesophageal echocardiography probes. Infect Control Hosp Epidemiol. 2003;24:619–22.PubMedCrossRefGoogle Scholar
  11. 11.
    Cooksey RC, Jhung MA, Yakrus MA, Butler WR, Adekambi T, Morlock GP, et al. Multiphasic approach reveals genetic diversity of environmental and patient isolates of Mycobacterium mucogenicum and Mycobacterium phocaicum associated with an outbreak of bacteremias at a Texas hospital. Appl Environ Microbiol. 2008;74:2480–7.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Kline S, Cameron S, Streifel A, Yakrus MA, Kairis F, Peacock K, et al. An outbreak of bacteremias associated with Mycobacterium mucogenicum in a hospital water supply. Infect Control Hosp Epidemiol. 2004;25:1042–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Ferroni A, Nguyen L, Pron B, Quesne G, Brusset MC, Berche P. Outbreak of nosocomial urinary tract infections due to Pseudomonas aeruginosa in a paediatric surgical unit associated with tap-water contamination. J Hosp Infect. 1998;39:301–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Hota S, Hirji Z, Stockton K, Lemieux C, Dedier H, Wolfaardt G, et al. Outbreak of multidrug-resistant Pseudomonas aeruginosa colonization and infection secondary to imperfect intensive care unit room design. Infect Control Hosp Epidemiol. 2009;30:25–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Johansson E, Welinder-Olsson C, Gilljam M. Genotyping of Pseudomonas aeruginosa isolates from lung transplant recipients and aquatic environment-detected in-hospital transmission. APMIS. 2014;122:85–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Davies D. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov. 2003;2:114–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Simoes M, Simoes LC, Vieira MJ. Species association increases biofilm resistance to chemical and mechanical treatments. Water Res. 2009;43:229–37.PubMedCrossRefGoogle Scholar
  18. 18.
    Palmore TN, Stock F, White M, Bordner M, Michelin A, Bennett JE, et al. A cluster of cases of nosocomial legionnaires disease linked to a contaminated hospital decorative water fountain. Infect Control Hosp Epidemiol. 2009;30:764–8.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Vergara-Lopez S, Dominguez MC, Conejo MC, Pascual A, Rodriguez-Bano J. Wastewater drainage system as an occult reservoir in a protracted clonal outbreak due to metallo-beta-lactamase-producing Klebsiella oxytoca. Clin Microbiol Infect. 2013;19:E490–8.PubMedGoogle Scholar
  20. 20.
    Halabi M, Wiesholzer-Pittl M, Schoberl J, Mittermayer H. Non-touch fittings in hospitals: a possible source of Pseudomonas aeruginosa and Legionella spp. J Hosp Infect. 2001;49:117–21.PubMedCrossRefGoogle Scholar
  21. 21.
    van der Mee-Marquet N, Bloc D, Briand L, Besnier JM, Quentin R. Non-touch fittings in hospitals: a procedure to eradicate Pseudomonas aeruginosa contamination. J Hosp Infect. 2005;60:235–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Sydnor ER, Bova G, Gimburg A, Cosgrove SE, Perl TM, Maragakis LL. Electronic-eye faucets: Legionella species contamination in healthcare settings. Infect Control Hosp Epidemiol. 2012;33:235–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Kotsanas D, Brett J, Kidd TJ, Stuart RL, Korman TM. Disinfection of Burkholderia cepacia complex from non-touch taps in a neonatal nursery. J Perinat Med. 2008;36:235–9.PubMedCrossRefGoogle Scholar
  24. 24.
    TE Haupt HR, Kazmierczak JJ, Nehls-Lowe H, Rheineck B, Powell C, Leonhardt KK, et al. An outbreak of Legionnaires disease associated with a decorative water wall fountain in a hospital. Infect Control Hosp Epidemiol. 2012;33:185–91.PubMedCrossRefGoogle Scholar
  25. 25.
    Armed Forces Health Surveillance Center (AFHSC). Legionellosis in Military Health System beneficiaries, 1998–2013. MSMR. 2014;21:6–9.Google Scholar
  26. 26.
    Zhou ZY, Hu B, Qin L, Lin YE, Watanabe H, Zhou Q, et al. Removal of waterborne pathogens from liver transplant unit water taps in prevention of healthcare-associated infections: a proposal for a cost-effective, proactive infection control strategy. Clin Microbiol Infect. 2014;20:310–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Richet H. Seasonality in Gram-negative and healthcare-associated infections. Clin Microbiol Infect. 2012;18:934–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Campins M, Ferrer A, Callis L, Pelaz C, Cortes PJ, Pinart N, et al. Nosocomial Legionnaire's disease in a children's hospital. Pediatr Infect Dis J. 2000;19:228–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Aringer M, Houssiau F, Gordon C, Graninger WB, Voll RE, Rath E, et al. Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients. Rheumatology (Oxford). 2009;48:1451–4.CrossRefGoogle Scholar
  30. 30.
    Kool JL, Fiore AE, Kioski CM, Brown EW, Benson RF, Pruckler JM, et al. More than 10 years of unrecognized nosocomial transmission of legionnaires' disease among transplant patients. Infect Control Hosp Epidemiol. 1998;19:898–904.PubMedCrossRefGoogle Scholar
  31. 31.
    Lepine LA, Jernigan DB, Butler JC, Pruckler JM, Benson RF, Kim G, et al. A recurrent outbreak of nosocomial legionnaires' disease detected by urinary antigen testing: evidence for long-term colonization of a hospital plumbing system. Infect Control Hosp Epidemiol. 1998;19:905–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Rudbeck M, Viskum S, Molbak K, Uldum SA. Legionella antibodies in a Danish hospital staff with known occupational exposure. J Environ Public Health. 2009;2009:812829.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Remen T, Mathieu L, Hautemaniere A, Deloge-Abarkan M, Hartemann P, Zmirou-Navier D. Pontiac fever among retirement home nurses associated with airborne Legionella. J Hosp Infect. 2011;78:269–73.PubMedCrossRefGoogle Scholar
  34. 34.
    Dominguez A, Alvarez J, Sabria M, Carmona G, Torner N, Oviedo M, et al. Factors influencing the case-fatality rate of Legionnaires' disease. Int J Tubercle Lung Dis. 2009;13:407–12.Google Scholar
  35. 35.
    Greub G, Raoult D. Microorganisms resistant to free-living amoebae. Clin Microbiol Rev. 2004;17:413–33.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Cervero-Arago S, Rodriguez-Martinez S, Canals O, Salvado H, Araujo RM. Effect of thermal treatment on free-living amoeba inactivation. J Appl Microbiol. 2013.Google Scholar
  37. 37.
    Centers for Disease Control and Prevention (CDC). Legionellosis --- United States, 2000-2009. MMWR Morb Mortal Wkly Rep. 2011;60(32):1083–6Google Scholar
  38. 38.
    Facility Guidelines Institute. Guidelines for design and construction of health care facilities. Chicago: American Society for Healthcare Engineering; 2014.Google Scholar
  39. 39.
    ASHRAE Standards Committee. Prevention of Legionellosis associated with building water systems. ASHRAE. 2011.Google Scholar
  40. 40.
    Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R, CDC, Healthcare Infection Control Practices Advisory Committee. Guidelines for preventing health-care–associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004;53(RR-3):1–36.Google Scholar
  41. 41.
    Snitkin ES, Zelazny AM, Thomas PJ, Stock F, Henderson DK, Palmore TN, et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med. 2012;4:148ra116.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Lowe C, Willey B, O'Shaughnessy A, Lee W, Lum M, Pike K, et al. Outbreak of extended-spectrum beta-lactamase-producing Klebsiella oxytoca infections associated with contaminated handwashing sinks(1). Emerg Infect Dis. 2012;18:1242–7.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Cristina ML, Spagnolo A, Casini B, Baggiani A, Del Giudice P, Brusaferro S, et al. The impact of aerators on water contamination by emerging gram-negative opportunists in at-risk hospital departments. Infect Control Hosp Epidemiol. 2014;35:122–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Gillespie TA, Johnson PR, Notman AW, Coia JE, Hanson MF. Eradication of a resistant Pseudomonas aeruginosa strain after a cluster of infections in a hematology/oncology unit. Clin Microbiol Infect. 2000;6:125–30.PubMedCrossRefGoogle Scholar
  45. 45.
    Sartor C, Limouzin PF, Legré R, Casanova D, Bongrand MC, Sambuc R, et al. Nosocomial infections with Aeromonas hydrophila from leeches. Clin Infect Dis. 2002;35:E1–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Wilmer A, Slater K, Yip J, Carr N, Grant J. The role of leech water sampling in choice of prophylactic antibiotics in medical leech therapy. Microsurgery. 2013;33:301–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Giltner CL, Bobenchik AM, Uslan DZ, Deville JG, Humphries RM. Ciprofloxacin-resistant Aeromonas hydrophila cellulitis following leech therapy. J Clin Microbiol. 2013;51:1324–6.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Crago B, Ferrato C, Drews SJ, Louie T, Ceri H, Turner RJ, et al. Surveillance and molecular characterization of non-tuberculous mycobacteria in a hospital water distribution system over a three-year period. J Hosp Infect. 2014;87:59–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Gebo KA, Srinivasan A, Perl TM, Ross T, Groth A, Merz WG. Pseudo-outbreak of Mycobacterium fortuitum on a human immunodeficiency virus ward: transient respiratory tract colonization from a contaminated ice machine. Clin Infect Dis. 2002;35:32–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Whiley H, Keegan A, Giglio S, Bentham R. Mycobacterium avium complex—the role of potable water in disease transmission. J Appl Microbiol. 2012;113:223–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Aronson T, Holtzman A, Glover N, Boian M, Froman S, Berlin OG, et al. Comparison of large restriction fragments of Mycobacterium avium isolates recovered from AIDS and non-AIDS patients with those of isolates from potable water. J Clin Microbiol. 1999;37:1008–12.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Tobin-D'Angelo MJ, Blass MA, del Rio C, Halvosa JS, Blumberg HM, Horsburgh Jr CR. Hospital water as a source of Mycobacterium avium complex isolates in respiratory specimens. J Infect Dis. 2004;189:98–104.PubMedCrossRefGoogle Scholar
  53. 53.
    Iroh Tam PY, Kline S, Wagner JE, Guspiel A, Streifel A, Ward G, et al. Rapidly growing mycobacteria among pediatric hematopoietic cell transplant patients traced to the hospital water supply. Pediatr Infect Dis J. 2014.Google Scholar
  54. 54.
    Brown-Elliott BA, Wallace Jr RJ, Tichindelean C, Sarria JC, McNulty S, Vasireddy R, et al. Five-year outbreak of community- and hospital-acquired Mycobacterium porcinum infections related to public water supplies. J Clin Microbiol. 2011;49:4231–8.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Wallace Jr RJ, Brown BA, Griffith DE. Nosocomial outbreaks/pseudo-outbreaks caused by nontuberculous mycobacteria. Annu Rev Microbiol. 1998;52:453–90.PubMedCrossRefGoogle Scholar
  56. 56.
    Anaissie EJ, Costa SF. Nosocomial aspergillosis is waterborne. Clin Infect Dis. 2001;33:1546–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Anaissie EJ, Kuchar RT, Rex JH, Francesconi A, Kasai M, Muller FM, et al. Fusariosis associated with pathogenic Fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mold infections. Clin Infect Dis. 2001;33:1871–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Anaissie EJ, Stratton SL, Dignani MC, Lee CK, Summerbell RC, Rex JH, et al. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies. Blood. 2003;101:2542–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Berger P, Papazian L, Drancourt M, La Scola B, Auffray JP, Raoult D. Ameba-associated microorganisms and diagnosis of nosocomial pneumonia. Emerg Infect Dis. 2006;12:248–55.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Panagopoulou P, Filioti J, Farmaki E, Maloukou A, Roilides E. Filamentous fungi in a tertiary care hospital: environmental surveillance and susceptibility to antifungal drugs. Infect Control Hosp Epidemiol. 2007;28:60–7.PubMedCrossRefGoogle Scholar
  61. 60.•
    Krageschmidt DA KA, Browning MS, Wright AJ, Lonneman JD, Detmer MJ, McCoy WF. A comprehensive water management program for multicampus healthcare facilities. Infect Control Hosp Epidemiol. 2014;35:556–63. Thorough description of a prospective water management plan in a complex healthcare system, providing a helpful roadmap for preventive management.PubMedCrossRefGoogle Scholar
  62. 62.
    Lin YE, Stout J, Yu VL. Controlling Legionella in hospital drinking water: an evidence-based review of disinfection methods. Infect Control Hosp Epidemiol. 2011;32:166–73.PubMedCrossRefGoogle Scholar
  63. 63.
    Marchesi IFG, Bargellini A, Marchegiano P, Predieri G, Stout JE, Borella P. Monochloramine and chlorine dioxide for controlling Legionella pneumophila contamination: biocide levels and disinfection by-product formation in hospital water networks. J Water Health. 2013;11:738–47.PubMedCrossRefGoogle Scholar
  64. 64.
    Kandiah S, Yassin MH, Stout J. Monochloramine use for prevention of Legionella in hospital water systems. Infect Disord Drug Targets. 2013;13:184–90.PubMedCrossRefGoogle Scholar
  65. 65.
    Comprehensive disinfectants and disinfection byproducts rules (Stage 1 and Stage 2). Environmental Protection Agency. 2006; 71.Google Scholar
  66. 66.
    Centers for Disease Control and Prevention. The CDC investigation of Legionnaires’ disease among patients at the VA Pittsburgh Healthcare System. 2013.Google Scholar
  67. 67.
    Casini B, Valentini P, Baggiani A, Torracca F, Frateschi S, Nelli LC, et al. Molecular epidemiology of Legionella pneumophila serogroup 1 isolates following long-term chlorine dioxide treatment in a university hospital water system. J Hosp Infect. 2008;69:141–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Casini B, Buzzigoli A, Cristina ML, Spagnolo AM, Del Giudice P, Brusaferro S, et al. Long-term effects of hospital water network disinfection on Legionella and other waterborne bacteria in an Italian university hospital. Infect Control Hosp Epidemiol. 2014;35:293–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Jakubek D, Guillaume C, Binet M, Leblon G, DuBow M, Le Brun M. Susceptibility of Legionella strains to the chlorinated biocide, monochloramine. Microbes Environ. 2013;28:336–45.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Johansson PJ, Andersson K, Wiebe T, Schalén C, Bernander S. Nosocomial transmission of Legionella pneumophila to a child from a hospital's cold-water supply. Scand J Infect Dis. 2006;38:1023–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Stout JE, Yu V, Muraca P. Isolation of Legionella pneumophila from the cold water of hospital ice machines: implications for origin and transmission of the organism. Infect Control. 1985;6:141–6.PubMedGoogle Scholar
  72. 72.
    Bencini MA, Yzerman E, Koornstra RH, Nolte CC, den Boer JW, Bruin JP. A case of Legionnaires' disease caused by aspiration of ice water. Arch Environ Occup Health. 2005;60:302–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Singh T, Coogan M. Isolation of pathogenic Legionella species and Legionella-laden amoebae in dental unit waterlines. J Hosp Infect. 2005;61:257–62.PubMedCrossRefGoogle Scholar
  74. 74.
    Lal S, Singhrao S, Bricknell M, Pearce M, Morton LH, Ahmed W, et al. Monitoring dental-unit-water-line output water by current in-office test kits. Curr Microbiol. 2014;69(2):135–42.PubMedCrossRefGoogle Scholar
  75. 75.
    Borella P, Bargellini A, Marchesi I, Rovesti S, Stancanelli G, Scaltriti S, et al. Prevalence of anti-Legionella antibodies among Italian hospital workers. J Hosp Infect. 2008;69:148–55.PubMedCrossRefGoogle Scholar
  76. 76.
    Chikte UM, Khondowe O, Gildenhuys I. A case study of a dental receptionist diagnosed with Legionnaires' disease. SADJ. 2011;66:284–7.PubMedGoogle Scholar
  77. 77.
    Epson EE, Pisney LM, Wendt JM, MacCannell DR, Janelle SJ, Kitchel B, et al. Carbapenem-resistant Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase at an acute care hospital, Colorado, 2012. Infect Control Hosp Epidemiol. 2014;35:390–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Witney AA, Gould KA, Pope CF, Bolt F, Stoker NG, Cubbon MD, et al. Genome sequencing and characterization of an extensively drug-resistant sequence type 111 serotype O12 hospital outbreak strain of Pseudomonas aeruginosa. Clin Microbiol Infect. 2014. doi: 10.1111/1469-0691.12528.
  79. 79.
    Kundu S, Lockwood J, Depledge DP, Chaudhry Y, Aston A, Rao K, et al. Next-generation whole genome sequencing identifies the direction of norovirus transmission in linked patients. Clin Infect Dis. 2013;57:407–14.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Reuter S, Harrison TG, Koser CU, Ellington MJ, Smith GP, Parkhill J, et al. A pilot study of rapid whole-genome sequencing for the investigation of a Legionella outbreak. BMJ Open. 2013;3:(1). doi: 10.1136/bmjopen-2012-002175.
  81. 81.
    Graham RM, Doyle CJ, Jennison AV. Real-time investigation of a Legionella pneumophila outbreak using whole genome sequencing. Epidemiol Infect. 2014;1–5. doi: 10.1017/S0950268814000375.
  82. 82.
    Yang JY, Brooks S, Meyer JA, Blakesley RR, Zelazny AM, Segre JA, et al. Pan-PCR, a computational method for designing bacterium-typing assays based on whole-genome sequence data. J Clin Microbiol. 2013;51:752–8.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  1. 1.National Institutes of Health Clinical CenterBethesdaUSA

Personalised recommendations