Controversies in Antimicrobial Stewardship

  • Graeme N. Forrest
Part of the Current Clinical Oncology book series (CCO)


Antimicrobial stewardship programs are ­recommended by the Infectious Diseases Society of America as a method to control antimicrobial costs and resistance. These programs are usually implemented hospital wide, but there is little evidence on their effects in oncology units. Three controversial areas of antimicrobial stewardship in oncology units include whether these programs decrease antimicrobial resistance when antimicrobial restriction is implemented, the role of antimicrobial cycling on Gram-negative resistance and that these programs rarely control outpatient antimicrobial therapy. This review will discuss these controversial areas with regard to the evidence, strength of trial design, and the generalizability of their outcomes.


Antimicrobial management Antimicrobial resistance Antibiotic cycling Outpatient antibiotic therapy VRE Clostridium difficile 


  1. 1.
    Schimpff S, Satterlee W, Young VM, Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971;284:1061–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982;72:101–11.PubMedCrossRefGoogle Scholar
  3. 3.
    Akova M, Paesmans M, Calandra T, Viscoli C. A European Organization for Research and Treatment of Cancer-International Antimicrobial Therapy Group Study of secondary infections in febrile, neutropenic patients with cancer. Clin Infect Dis. 2005;40:239–45.PubMedCrossRefGoogle Scholar
  4. 4.
    Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34:730–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Segal BH, Almyroudis NG, Battiwalla M, Herbrecht R, Perfect JR, Walsh TJ, et al. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin Infect Dis. 2007;44:402–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Cometta A, Viscoli C, Castagnola E, Massimo L, Giacchino R, Gibson B, et al. Empirical treatment of fever in neutropenic children: the role of the carbapenems. International Antimicrobial Therapy Cooperative Group of the European Organisation for Research and Treatment of Cancer and the Gimema Infection Program. Pediatr Infect Dis J. 1996;15:744–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Deshpande LM, Jones RN, Fritsche TR, Sader HS. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000–2004). Microb Drug Resist. 2006;12:223–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Ghanem G, Hachem R, Jiang Y, Chemaly RF, Raad I. Outcomes for and risk factors associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium bacteremia in cancer patients. Infect Control Hosp Epidemiol. 2007;28:1054–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Mutnick AH, Kirby JT, Jones RN. CANCER resistance surveillance program: initial results from hematology-oncology centers in North America. Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance. Ann Pharmacother. 2003;37:47–56.PubMedCrossRefGoogle Scholar
  10. 10.
    Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev. 2005;18:657–86.PubMedCrossRefGoogle Scholar
  11. 11.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG, Levine AS, Deisseroth AB, et al. Duration of empiric antibiotic therapy in granulocytopenic patients with cancer. Am J Med. 1979;67:194–200.PubMedCrossRefGoogle Scholar
  12. 12.
    Kollef MH. Providing appropriate antimicrobial therapy in the intensive care unit: surveillance vs. de-escalation. Crit Care Med. 2006;34:903–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Paterson DL, Rice LB. Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive? Clin Infect Dis. 2003;36:1006–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Hachem R, Graviss L, Hanna H, Arbuckle R, Dvorak T, Hackett B, et al. Impact of surveillance for vancomycin-resistant enterococci on controlling a bloodstream outbreak among patients with hematologic malignancy. Infect Control Hosp Epidemiol. 2004;25:391–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Montecalvo MA, Jarvis WR, Uman J, Shay DK, Petrullo C, Horowitz HW, et al. Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting. Infect Control Hosp Epidemiol. 2001;22:437–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Junior MS, Correa L, Marra AR, Camargo LF, Pereira CA. Analysis of vancomycin use and associated risk factors in a university teaching hospital: a prospective cohort study. BMC Infect Dis. 2007;7:88.PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt-Hieber M, Blau IW, Schwartz S, Uharek L, Weist K, Eckmanns T, et al. Intensified strategies to control vancomycin-resistant enterococci in immunocompromised patients. Int J Hematol. 2007;86:158–62.PubMedCrossRefGoogle Scholar
  18. 18.
    Worth LJ, Thursky KA, Seymour JF, Slavin MA. Vancomycin-resistant Enterococcus faecium infection in patients with hematologic malignancy: patients with acute myeloid leukemia are at high-risk. Eur J Haematol. 2007;79:226–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Zirakzadeh A, Gastineau DA, Mandrekar JN, Burke JP, Johnston PB, Patel R. Vancomycin-resistant enterococcal colonization appears associated with increased mortality among allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2008;41:385–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Zaas AK, Song X, Tucker P, Perl TM. Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. Clin Infect Dis. 2002;35:1139–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Lautenbach E, Bilker WB, Brennan PJ. Enterococcal bacteremia: risk factors for vancomycin resistance and predictors of mortality. Infect Control Hosp Epidemiol. 1999;20:318–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Lucas GM, Lechtzin N, Puryear DW, Yau LL, Flexner CW, Moore RD. Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes. Clin Infect Dis. 1998;26:1127–33.PubMedCrossRefGoogle Scholar
  23. 23.
    Fridkin SK, Lawton R, Edwards JR, Tenover FC, McGowan Jr JE, Gaynes RP. Monitoring antimicrobial use and resistance: comparison with a national benchmark on reducing vancomycin use and vancomycin-resistant enterococci. Emerg Infect Dis. 2002;8:702–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Dubberke ER, Hollands JM, Georgantopoulos P, Augustin K, Dipersio JF, Mundy LM, et al. Vancomycin-resistant enterococcal bloodstream infections on a hematopoietic stem cell transplant unit: are the sick getting sicker? Bone Marrow Transplant. 2006;38:813–9.PubMedCrossRefGoogle Scholar
  25. 25.
    de Bruin MA, Riley LW. Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review. BMC Infect Dis. 2007;7:24.PubMedCrossRefGoogle Scholar
  26. 26.
    Harris AD, Lautenbach E, Perencevich E. A systematic review of quasi-experimental study designs in the fields of infection control and antibiotic resistance. Clin Infect Dis. 2005;41:77–82.PubMedCrossRefGoogle Scholar
  27. 27.
    Lautenbach E, LaRosa LA, Marr AM, Nachamkin I, Bilker WB, Fishman NO. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Clin Infect Dis. 2003;36:440–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Morris Jr JG, Shay DK, Hebden JN, McCarter Jr RJ, Perdue BE, Jarvis W, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center. Ann Intern Med. 1995;123:250–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Rubin LG, Tucci V, Cercenado E, Eliopoulos G, Isenberg HD. Vancomycin-resistant Enterococcus faecium in hospitalized children. Infect Control Hosp Epidemiol. 1992;13:700–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Quale J, Landman D, Saurina G, Atwood E, Ditore V, Patel K. Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis. 1996;23:1020–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Anglim AM, Klym B, Byers KE, Scheld WM, Farr BM. Effect of a vancomycin restriction policy on ordering practices during an outbreak of vancomycin-resistant Enterococcus faecium. Arch Intern Med. 1997;157:1132–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Lai KK. Control of vancomycin-resistant enterococcus. Ann Intern Med. 1997;126:1000–1.PubMedCrossRefGoogle Scholar
  33. 33.
    Shaikh ZH, Osting CA, Hanna HA, Arbuckle RB, Tarr JJ, Raad II. Effectiveness of a multifaceted infection control policy in reducing vancomycin usage and vancomycin-resistant enterococci at a tertiary care cancer centre. J Hosp Infect. 2002;51:52–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Patel D, Lawson W, Guglielmo BJ. Antimicrobial stewardship programs: interventions and associated outcomes. Expert Rev Anti Infect Ther. 2008;6:209–22.PubMedCrossRefGoogle Scholar
  35. 35.
    Guglielmo BJ, Dudas V, Maewal I, Young R, Hilts A, Villmann M, et al. Impact of a series of interventions in vancomycin prescribing on use and prevalence of vancomycin-resistant enterococci. Jt Comm J Qual Patient Saf. 2005;31:469–75.PubMedGoogle Scholar
  36. 36.
    Byers KE, Anglim AM, Anneski CJ, Germanson TP, Gold HS, Durbin LJ, et al. A hospital epidemic of vancomycin-resistant Enterococcus: risk factors and control. Infect Control Hosp Epidemiol. 2001;22:140–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Noskin GA. Vancomycin-resistant enterococci: clinical, microbiologic, and epidemiologic features. J Lab Clin Med. 1997;130:14–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Paterson DL, Muto CA, Ndirangu M, Linden PK, Potoski BA, Capitano B, et al. Acquisition of rectal colonization by vancomycin-resistant Enterococcus among intensive care unit patients treated with piperacillin-tazobactam versus those receiving cefepime-containing antibiotic regimens. Antimicrob Agents Chemother. 2008;52:465–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Palmore TN, Sohn S, Malak SF, Eagan J, Sepkowitz KA. Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital. Infect Control Hosp Epidemiol. 2005;26:680–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Blot E, Escande MC, Besson D, Barbut F, Granpeix C, Asselain B, et al. Outbreak of Clostridium difficile-related diarrhoea in an adult oncology unit: risk factors and microbiological characteristics. J Hosp Infect. 2003;53:187–92.PubMedCrossRefGoogle Scholar
  41. 41.
    Pepin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41:1254–60.PubMedCrossRefGoogle Scholar
  42. 42.
    Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353:2442–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Muto CA, Blank MK, Marsh JW, Vergis EN, O’Leary MM, Shutt KA, et al. Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive “bundle” approach. Clin Infect Dis. 2007;45:1266–73.PubMedCrossRefGoogle Scholar
  45. 45.
    Khan R, Cheesbrough J. Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital. J Hosp Infect. 2003;54:104–8.PubMedCrossRefGoogle Scholar
  46. 46.
    McNulty C, Logan M, Donald IP, Ennis D, Taylor D, Baldwin RN, et al. Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy. J Antimicrob Chemother. 1997;40:707–11.PubMedCrossRefGoogle Scholar
  47. 47.
    Muto CA, Pokrywka M, Shutt K, Mendelsohn AB, Nouri K, Posey K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a ­teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005;26:273–80.PubMedCrossRefGoogle Scholar
  48. 48.
    Pepin J. Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic? Clin Infect Dis. 2008;46:1493–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Brahmi N, Blel Y, Kouraichi N, Lahdhiri S, Thabet H, Hedhili A, et al. Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit. J Infect Chemother. 2006;12:190–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Lautenbach E, Metlay JP, Bilker WB, Edelstein PH, Fishman NO. Association between fluoroquinolone resistance and mortality in Escherichia coli and Klebsiella pneumoniae infections: the role of inadequate empirical antimicrobial therapy. Clin Infect Dis. 2005;41:923–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Lautenbach E, Weiner MG, Nachamkin I, Bilker WB, Sheridan A, Fishman NO. Imipenem resistance among Pseudomonas aeruginosa isolates: risk factors for infection and impact of resistance on clinical and economic outcomes. Infect Control Hosp Epidemiol. 2006;27:893–900.PubMedCrossRefGoogle Scholar
  52. 52.
    Patterson JE. Multidrug-resistant gram-negative pathogens: multiple approaches and measures for prevention. Infect Control Hosp Epidemiol. 2006;27:889–92.PubMedCrossRefGoogle Scholar
  53. 53.
    Pitout JD, Le P, Church DL, Gregson DB, Laupland KB. Antimicrobial susceptibility of well-characterised multiresistant CTX-M-producing Escherichia coli: failure of automated systems to detect resistance to piperacillin/tazobactam. Int J Antimicrob Agents. 2008;32:333–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Poirel L, Pitout JD, Nordmann P. Carbapenemases: molecular diversity and clinical consequences. Future Microbiol. 2007;2:501–12.PubMedCrossRefGoogle Scholar
  55. 55.
    Rolston KV. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis. 2005;40 Suppl 4:S246–52.PubMedCrossRefGoogle Scholar
  56. 56.
    Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1–12.PubMedCrossRefGoogle Scholar
  57. 57.
    Zinner SH. Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria. Clin Infect Dis. 1999;29:490–4.PubMedCrossRefGoogle Scholar
  58. 58.
    Hachem RY, Chemaly RF, Ahmar CA, Jiang Y, Boktour MR, Rjaili GA, et al. Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients. Antimicrob Agents Chemother. 2007;51:1905–11.PubMedCrossRefGoogle Scholar
  59. 59.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24, 179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–17.PubMedCrossRefGoogle Scholar
  60. 60.
    Glasmacher A, von Lilienfeld-Toal M, Schulte S, Hahn C, Schmidt-Wolf IG, Prentice A. An evidence-based evaluation of important aspects of empirical antibiotic therapy in febrile neutropenic patients. Clin Microbiol Infect. 2005;11 Suppl 5:17–23.PubMedCrossRefGoogle Scholar
  61. 61.
    Safdar A, Rodriguez GH, Balakrishnan M, Tarrand JJ, Rolston KV. Changing trends in etiology of bacteremia in patients with cancer. Eur J Clin Microbiol Infect Dis. 2006;25:522–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis. 2008;46:567–70.PubMedCrossRefGoogle Scholar
  63. 63.
    Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis. 2007;45:1179–81.PubMedCrossRefGoogle Scholar
  64. 64.
    Gerding DN, Larson TA. Aminoglycoside resistance in gram-negative bacilli during increased amikacin use. Comparison of experience in 14 United States hospitals with experience in the Minneapolis Veterans Administration Medical Center. Am J Med. 1985;79:1–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Brown EM, Nathwani D. Antibiotic cycling or rotation: a systematic review of the evidence of efficacy. J Antimicrob Chemother. 2005;55:6–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Gasink LB, Fishman NO, Weiner MG, Nachamkin I, Bilker WB, Lautenbach E. Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact. Am J Med. 2006;119(526):e19–25.PubMedGoogle Scholar
  67. 67.
    Paterson DL. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis. 2006;43 Suppl 2:S43–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Cadena J, Taboada CA, Burgess DS, Ma JZ, Lewis JS, Freytes CO, et al. Antibiotic cycling to decrease bacterial antibiotic resistance: a 5-year experience on a bone marrow transplant unit. Bone Marrow Transplant. 2007;40:151–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Craig M, Cumpston AD, Hobbs GR, Devetten MP, Sarwari AR, Ericson SG. The clinical impact of antibacterial prophylaxis and cycling antibiotics for febrile neutropenia in a hematological malignancy and transplantation unit. Bone Marrow Transplant. 2007;39:477–82.PubMedCrossRefGoogle Scholar
  70. 70.
    Dominguez EA, Smith TL, Reed E, Sanders CC, Sanders Jr WE. A pilot study of antibiotic cycling in a hematology-oncology unit. Infect Control Hosp Epidemiol. 2000;21:S4–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Bradley SJ, Wilson AL, Allen MC, Sher HA, Goldstone AH, Scott GM. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage. J Antimicrob Chemother. 1999;43:261–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Masterton RG. Antibiotic cycling: more than it might seem? J Antimicrob Chemother. 2005;55:1–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Rolston KV. New trends in patient management: risk-based therapy for febrile patients with neutropenia. Clin Infect Dis. 1999;29:515–21.PubMedCrossRefGoogle Scholar
  74. 74.
    Talcott JA, Whalen A, Clark J, Rieker PP, Finberg R. Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: a pilot study of 30 patients based on a validated prediction rule. J Clin Oncol. 1994;12:107–14.PubMedGoogle Scholar
  75. 75.
    Talcott JA, Finberg R, Mayer RJ, Goldman L. The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Arch Intern Med. 1988;148:2561–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Freifeld A, Marchigiani D, Walsh T, Chanock S, Lewis L, Hiemenz J, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med. 1999;341:305–11.PubMedCrossRefGoogle Scholar
  77. 77.
    Kern WV. Outpatient management in patients with neutropenia after intensive chemotherapy – is it safe? Ann Oncol. 2005;16:179–80.PubMedCrossRefGoogle Scholar
  78. 78.
    Kern WV, Steib-Bauert M, de With K, Reuter S, Bertz H, Frank U, et al. Fluoroquinolone consumption and resistance in haematology-oncology patients: ecological analysis in two university hospitals 1999–2002. J Antimicrob Chemother. 2005;55:57–60.PubMedCrossRefGoogle Scholar
  79. 79.
    Mueller MR, Hayden MK, Fridkin SK, Warren DK, Phillips L, Lolans K, et al. Nosocomial acquisition of Pseudomonas aeruginosa resistant to both ciprofloxacin and imipenem: a risk factor and laboratory analysis. Eur J Clin Microbiol Infect Dis. 2008;27:565–70.PubMedCrossRefGoogle Scholar
  80. 80.
    Kern WV, Klose K, Jellen-Ritter AS, Oethinger M, Bohnert J, Kern P, et al. Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia. Eur J Clin Microbiol Infect Dis. 2005;24:111–18.PubMedCrossRefGoogle Scholar
  81. 81.
    Thom KA, Schweizer ML, Osih RB, McGregor JC, Furuno JP, Perencevich EN, et al. Impact of empiric antimicrobial therapy on outcomes in patients with Escherichia coli and Klebsiella pneumoniae bacteremia: a cohort study. BMC Infect Dis. 2008;8:116.PubMedCrossRefGoogle Scholar
  82. 82.
    Tacconelli E, Tumbarello M, Bertagnolio S, Citton R, Spanu T, Fadda G, et al. Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: analysis of trends in prevalence and epidemiology. Emerg Infect Dis. 2002;8:220–1.PubMedCrossRefGoogle Scholar
  83. 83.
    Nicasio AM, Kuti JL, Nicolau DP. The current state of multidrug-resistant gram-negative bacilli in North America. Pharmacotherapy. 2008;28:235–49.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Infectious DiseasePortland VA Medical CenterPortlandUSA

Personalised recommendations