Gram-Positive Bacterial Infections After Haematopoietic Stem Cell or Solid Organ Transplantation

  • Malgorzata Mikulska
  • Claudio Viscoli


Infections due to Gram-positive bacteria are frequent after transplantation, and they occur mainly in the early post-transplant period. Predisposing conditions include neutropenia, particularly after haematopoietic stem cell transplant (HSCT), and mechanical defence impairment related to surgery and ICU stay after solid organ transplant (SOT). Central venous catheters are involved in both settings. Bacteraemias and pneumonia are more frequent in HSCT recipients while localised infections (mediastinitis, pneumonia, cholangitis, abscesses), particularly enterococcal, are more prevalent after SOT. Coagulase-negative staphylococci, enterococci and viridans streptococci are typical Gram-positive pathogens during pre-engraftment bacteraemia after HSCT, while Staphylococcus aureus and enterococci are more frequent among SOT recipients. The mortality rate is variable, and usually lower than in Gram-negative or fungal infections. In late post-transplant phases, the risk of pneumococcal infection is high.

Although widely used, an empiric anti-Gram positive coverage should not be the rule in febrile neutropenic patients undergoing HSCT, unless specific risk factors are present. In SOT no specific rule for empirical therapy has ever been established. Antibiotic resistance is not infrequent in Gram-positive bacteria, with high rate of methicillin resistance. Fortunately, new drugs are available for treating resistant Gram-positive infections.


Bone marrow transplant Solid organ transplant Gram positive Staphylococcus Enterococci VRE Viridans streptococci Empirical therapy Vancomycin Daptomycin Linezolid 


  1. 1.
    Viscoli C, Castagnola E. Treatment of febrile neutropenia: what is new? Curr Opin Infect Dis. 2002;15(4):377–82.PubMedCrossRefGoogle Scholar
  2. 2.
    Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003;36(9):1103–10.PubMedCrossRefGoogle Scholar
  3. 3.
    EORTC International Antimicrobial Therapy Cooperative Group. Gram-positive bacteraemia in granulocytopenic cancer patients. Eur J Cancer. 1990;26(5):569–74.CrossRefGoogle Scholar
  4. 4.
    Klastersky J. Science and pragmatism in the treatment and prevention of neutropenic infection. J Antimicrob Chemother. 1998;41(Suppl D):13–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Aksu G, Ruhi MZ, Akan H, Bengisun S, Ustun C, Arslan O, et al. Aerobic bacterial and fungal infections in peripheral blood stem cell transplants. Bone Marrow Transplant. 2001;27(2):201–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Cappellano P, Viscoli C, Bruzzi P, Van Lint MT, Pereira CA, Bacigalupo A. Epidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantation. New Microbiol. 2007;30(2):89–99.PubMedGoogle Scholar
  7. 7.
    Haupt R, Romanengo M, Fears T, Viscoli C, Castagnola E. Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours: a 12-year experience at a single Italian institution. Eur J Cancer. 2001;37(18):2413–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis. 2001;33(7):947–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Cometta A, Kern WV, De Bock R, Paesmans M, Vandenbergh M, Crokaert F, et al. Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy. Clin Infect Dis. 2003;37(3):382–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Ortega M, Rovira M, Almela M, Marco F, de la Bellacasa JP, Martinez JA, et al. Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol. 2005;84(1):40–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, et al. Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother. 2008;61(3):721–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Chong Y, Yakushiji H, Ito Y, Kamimura T. Cefepime-resistant gram-negative bacteremia in febrile neutropenic patients with hematological malignancies. Int J Infect Dis. 2010;14 Suppl 3:e171–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Mikulska M, Del Bono V, Raiola AM, Bruno B, Gualandi F, Occhini D, et al. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant. 2009;15(1):47–53.PubMedCrossRefGoogle Scholar
  14. 14.
    Oliveira AL, de Souza M, Carvalho-Dias VM, Ruiz MA, Silla L, Tanaka PY, et al. Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2007;39(12):775–81.PubMedCrossRefGoogle Scholar
  15. 15.
    Jacobson K, Rolston K, Elting L, LeBlanc B, Whimbey E, Ho DH. Susceptibility surveillance among gram-negative bacilli at a cancer center. Chemotherapy. 1999;45(5):325–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Kamboj M, Chung D, Seo SK, Pamer EG, Sepkowitz KA, Jakubowski AA, et al. The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transplant. 2010;16(11):1576–81.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Gudiol C, Bodro M, Simonetti A, Tubau F, Gonzalez-Barca E, Cisnal M, et al. Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect. 2013;19(5):474–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen CY, Tsay W, Tang JL, Tien HF, Chen YC, Chang SC, et al. Epidemiology of bloodstream infections in patients with haematological malignancies with and without neutropenia. Epidemiol Infect. 2010;138(7):1044–51.PubMedCrossRefGoogle Scholar
  19. 19.
    Mikulska M, Viscoli C, Orasch C, Livermore DM, Averbuch D, Cordonnier C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect. 2014;68(4):321–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Sood P, Seth T, Kapil A, Sharma V, Dayama A, Sharma S, et al. Emergence of multidrug resistant acinetobacter blood stream infections in febrile neutropenia patients with haematological cancers and bone marrow failure syndromes. J Indian Med Assoc. 2012;110(7):439–44.PubMedGoogle Scholar
  21. 21.
    Bucaneve G, Micozzi A, Picardi M, Ballanti S, Cascavilla N, Salutari P, et al. Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia. J Clin Oncol. 2014;32(14):1463–71.PubMedCrossRefGoogle Scholar
  22. 22.
    Shaw BE, Boswell T, Byrne JL, Yates C, Russell NH. Clinical impact of MRSA in a stem cell transplant unit: analysis before, during and after an MRSA outbreak. Bone Marrow Transplant. 2007;39(10):623–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Quilty S, Kwok G, Hajkowicz K, Currie B. High incidence of methicillin-resistant Staphylococcus aureus sepsis and death in patients with febrile neutropenia at Royal Darwin Hospital. Intern Med J. 2009;39(8):557–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedCrossRefGoogle Scholar
  25. 25.
    Tacconelli E. Methicillin-resistant Staphylococcus aureus: source control and surveillance organization. Clin Microbiol Infect. 2009;15 Suppl 7:31–8.PubMedCrossRefGoogle Scholar
  26. 26.
    ECDC. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2012. Annual report of the European antimicrobial resistance surveillance network (EARS-Net). Stockholm: ECDC; 2013.
  27. 27.
    Livermore DM. Fourteen years in resistance. Int J Antimicrob Agents. 2012;39(4):283–94.PubMedCrossRefGoogle Scholar
  28. 28.
    Rodvold KA, McConeghy KW. Methicillin-resistant Staphylococcus aureus therapy: past, present, and future. Clin Infect Dis. 2014;58 Suppl 1:S20–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Mikulska M, Del Bono V, Prinapori R, Boni L, Raiola AM, Gualandi F, et al. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2010;12(6):505–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Macesic N, Morrissey CO, Cheng AC, Spencer A, Peleg AY. Changing microbial epidemiology in hematopoietic stem cell transplant recipients: increasing resistance over a 9-year period. Transpl Infect Dis. 2014;16(6):887–96.PubMedCrossRefGoogle Scholar
  31. 31.
    Tavadze M, Rybicki L, Mossad S, Avery R, Yurch M, Pohlman B, et al. Risk factors for vancomycin-resistant enterococcus bacteremia and its influence on survival after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2014;49(10):1310–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Bow EJ. Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis. 2011;24(6):545–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Blennow O, Ljungman P, Sparrelid E, Mattsson J, Remberger M. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis. 2014;16(1):106–14.PubMedCrossRefGoogle Scholar
  34. 34.
    Gudiol C, Ayats J, Camoez M, Dominguez MA, Garcia-Vidal C, Bodro M, et al. Increase in bloodstream infection due to vancomycin-susceptible Enterococcus faecium in cancer patients: risk factors, molecular epidemiology and outcomes. PLoS One. 2013;8(9):e74734.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Avery R, Kalaycio M, Pohlman B, Sobecks R, Kuczkowski E, Andresen S, et al. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course. Bone Marrow Transplant. 2005;35(5):497–9.PubMedCrossRefGoogle Scholar
  36. 36.
    DiazGranados CA, Jernigan JA. Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection. J Infect Dis. 2005;191(4):588–95.PubMedCrossRefGoogle Scholar
  37. 37.
    Kjellander C, Bjorkholm M, Cherif H, Kalin M, Giske CG. Hematological: low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study. Eur J Haematol. 2012;88(5):422–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Caballero-Granado FJ, Becerril B, Cuberos L, Bernabeu M, Cisneros JM, Pachon J. Attributable mortality rate and duration of hospital stay associated with enterococcal bacteremia. Clin Infect Dis. 2001;32(4):587–94.PubMedCrossRefGoogle Scholar
  39. 39.
    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(12):813–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Cho SY, Lee DG, Choi SM, Kwon JC, Kim SH, Choi JK, et al. Impact of vancomycin resistance on mortality in neutropenic patients with enterococcal bloodstream infection: a retrospective study. BMC Infect Dis. 2013;13:504.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lisboa LF, Miranda BG, Vieira MB, Dulley FL, Fonseca GG, Guimaraes T, et al. Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant Enterococcus spp. Int J Infect Dis. 2015;33:171–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Mikulska M, Del Bono V, Raiola AM, Signori A, Prinapori R, Ghiso A, et al. Enterococcal bloodstream infection after hematopoietic stem cell transplant: experience of a center with a low prevalence of vancomycin-resistant enterococci. Clin Infect Dis. 2012;55(12):1744.PubMedCrossRefGoogle Scholar
  43. 43.
    Vydra J, Shanley RM, George I, Ustun C, Smith AR, Weisdorf DJ, et al. Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55(6):764–70.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Weinstock DM, Conlon M, Iovino C, Aubrey T, Gudiol C, Riedel E, et al. Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2007;13(5):615–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Balli EP, Venetis CA, Miyakis S. Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia. Antimicrob Agents Chemother. 2014;58(2):734–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Chuang YC, Wang JT, Lin HY, Chang SC. Daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bacteremia: systematic review and meta-analysis. BMC Infect Dis. 2014;14:687.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Whang DW, Miller LG, Partain NM, McKinnell JA. Systematic review and meta-analysis of linezolid and daptomycin for treatment of vancomycin-resistant enterococcal bloodstream infections. Antimicrob Agents Chemother. 2013;57(10):5013–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Britt NS, Potter EM, Patel N, Steed ME. Comparison of the effectiveness and safety of linezolid and daptomycin in vancomycin-resistant enterococcal bloodstream infection: a national cohort study of veterans affairs patients. Clin Infect Dis. 2015;61(6):871–8.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Bradley JS. Which antibiotic for resistant Gram-positives, and why? J Infect. 2014;68 Suppl 1:S63–75.PubMedCrossRefGoogle Scholar
  50. 50.
    Shenep JL. Viridans-group streptococcal infections in immunocompromised hosts. Int J Antimicrob Agents. 2000;14(2):129–35.PubMedCrossRefGoogle Scholar
  51. 51.
    Freifeld AG, Razonable RR. Viridans group streptococci in febrile neutropenic cancer patients: what should we fear? Clin Infect Dis. 2014;59(2):231–3.PubMedCrossRefGoogle Scholar
  52. 52.
    Dompeling EC, Donnelly JP, Raemaekers JM, De Pauw BE. Pre-emptive administration of corticosteroids prevents the development of ARDS associated with Streptococcus mitis bacteremia following chemotherapy with high-dose cytarabine. Ann Hematol. 1994;69(2):69–71.PubMedCrossRefGoogle Scholar
  53. 53.
    Yacoub AT, Mojica L, Jones L, Knab A, Alrabaa S, Greene J. The role of corticosteroids in adult respiratory distress syndrome caused by viridans group streptococci bacteremia in neutropenic patients. Mediterr J Hematol Infect Dis. 2014;6(1), e2014055.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Han XY, Kamana M, Rolston KV. Viridans streptococci isolated by culture from blood of cancer patients: clinical and microbiologic analysis of 50 cases. J Clin Microbiol. 2006;44(1):160–5.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Elting LS, Rubenstein EB, Rolston KV, Bodey GP. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clin Infect Dis. 1997;25(2):247–59.PubMedCrossRefGoogle Scholar
  56. 56.
    Shenep JL, Hughes WT, Roberson PK, Blankenship KR, Baker Jr DK, Meyer WH, et al. Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer. N Engl J Med. 1988;319(16):1053–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Shelburne 3rd SA, Lasky RE, Sahasrabhojane P, Tarrand JT, Rolston KV. Development and validation of a clinical model to predict the presence of beta-lactam resistance in viridans group streptococci causing bacteremia in neutropenic cancer patients. Clin Infect Dis. 2014;59(2):223–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):427–31.PubMedCrossRefGoogle Scholar
  59. 59.
    Kulkarni S, Powles R, Treleaven J, Riley U, Singhal S, Horton C, et al. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants. Blood. 2000;95(12):3683–6.PubMedGoogle Scholar
  60. 60.
    Engelhard D, Cordonnier C, Shaw PJ, Parkalli T, Guenther C, Martino R, et al. Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey. Br J Haematol. 2002;117(2):444–50.PubMedCrossRefGoogle Scholar
  61. 61.
    Kumar D, Humar A, Plevneshi A, Siegal D, Franke N, Green K, et al. Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: a decade of prospective population-based surveillance. Bone Marrow Transplant. 2008;41(8):743–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Torda A, Chong Q, Lee A, Chen S, Dodds A, Greenwood M, et al. Invasive pneumococcal disease following adult allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2014;16(5):751–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Gudiol C, Garcia-Vidal C, Arnan M, Sanchez-Ortega I, Patino B, Duarte R, et al. Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. Bone Marrow Transplant. 2014;49(6):824–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Castagnola E, Fioredda F. Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur J Haematol. 2003;71(5):319–26.PubMedCrossRefGoogle Scholar
  66. 66.
    Yoo JH, Lee DG, Choi SM, Choi JH, Park YH, Kim YJ, et al. Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea. Bone Marrow Transplant. 2004;34(6):497–504.PubMedCrossRefGoogle Scholar
  67. 67.
    Dettenkofer M, Wenzler-Rottele S, Babikir R, Bertz H, Ebner W, Meyer E, et al. Surveillance of nosocomial sepsis and pneumonia in patients with a bone marrow or peripheral blood stem cell transplant: a multicenter project. Clin Infect Dis. 2005;40(7):926–31.PubMedCrossRefGoogle Scholar
  68. 68.
    Yamasaki S, Heike Y, Mori S, Fukuda T, Maruyama D, Kato R, et al. Infectious complications in chronic graft-versus-host disease: a retrospective study of 145 recipients of allogeneic hematopoietic stem cell transplantation with reduced- and conventional-intensity conditioning regimens. Transpl Infect Dis. 2008;10(4):252–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Forslow U, Mattsson J, Ringden O, Klominek J, Remberger M. Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation. Scand J Infect Dis. 2006;38(11–12):970–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Gentile G, Micozzi A, Girmenia C, Iori AP, Donati PP, Capria S, et al. Pneumonia in allogenic and autologous bone marrow recipients. A retrospective study. Chest. 1993;104(2):371–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Lucena CM, Torres A, Rovira M, Marcos MA, de la Bellacasa JP, Sanchez M, et al. Pulmonary complications in hematopoietic SCT: a prospective study. Bone Marrow Transplant. 2014;49(10):1293–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Yamshchikov AV, Schuetz A, Lyon GM. Rhodococcus equi infection. Lancet Infect Dis. 2010;10(5):350–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Forslow U, Remberger M, Nordlander A, Mattsson J. The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia. Bone Marrow Transplant. 2010;45(5):945–50.PubMedCrossRefGoogle Scholar
  74. 74.
    Shannon VR, Andersson BS, Lei X, Champlin RE, Kontoyiannis DP. Utility of early versus late fiberoptic bronchoscopy in the evaluation of new pulmonary infiltrates following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45(4):647–55.PubMedCrossRefGoogle Scholar
  75. 75.
    Aguilar-Guisado M, Jimenez-Jambrina M, Espigado I, Rovira M, Martino R, Oriol A, et al. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. Clin Transplant. 2011;25(6):E629–38.PubMedCrossRefGoogle Scholar
  76. 76.
    Alangaden GJ, Wahiduzzaman M, Chandrasekar PH, Bone Marrow Transplant Group. Aspergillosis: the most common community-acquired pneumonia with gram-negative Bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease. Clin Infect Dis. 2002;35(6):659–64.PubMedCrossRefGoogle Scholar
  77. 77.
    Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357(25):2601–14.PubMedCrossRefGoogle Scholar
  78. 78.
    Bucheli E, Kralidis G, Boggian K, Cusini A, Garzoni C, Manuel O, et al. Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study. Transpl Infect Dis. 2014;16(1):26–36.PubMedCrossRefGoogle Scholar
  79. 79.
    Wagener MM, Yu VL. Bacteremia in transplant recipients: a prospective study of demographics, etiologic agents, risk factors, and outcomes. Am J Infect Control. 1992;20(5):239–47.PubMedCrossRefGoogle Scholar
  80. 80.
    San Juan R, Aguado JM, Lumbreras C, Diaz-Pedroche C, Lopez-Medrano F, Lizasoain M, et al. Incidence, clinical characteristics and risk factors of late infection in solid organ transplant recipients: data from the RESITRA study group. Am J Transplant. 2007;7(4):964–71.PubMedCrossRefGoogle Scholar
  81. 81.
    Malinis MF, Mawhorter SD, Jain A, Shrestha NK, Avery RK, van Duin D. Staphylococcus aureus bacteremia in solid organ transplant recipients: evidence for improved survival when compared with nontransplant patients. Transplantation. 2012;93(10):1045–50.PubMedCrossRefGoogle Scholar
  82. 82.
    Zhou J, Huang H, Liu S, Yu P, Wan Q. Staphylococcus aureus bacteremias following liver transplantation: a clinical analysis of 20 cases. Ther Clin Risk Manag. 2015;11:933–7.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Eyuboglu FO, Kupeli E, Bozbas SS, Ozen ZE, Akkurt ES, Aydogan C, et al. Evaluation of pulmonary infections in solid organ transplant patients: 12 years of experience. Transplant Proc. 2013;45(10):3458–61.PubMedCrossRefGoogle Scholar
  84. 84.
    Ziakas PD, Pliakos EE, Zervou FN, Knoll BM, Rice LB, Mylonakis E. MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies. Am J Transplant. 2014;14(8):1887–94.PubMedCrossRefGoogle Scholar
  85. 85.
    Kim YJ, Kim SI, Wie SH, Kim YR, Hur JA, Choi JY, et al. Infectious complications in living-donor liver transplant recipients: a 9-year single-center experience. Transpl Infect Dis. 2008;10(5):316–24.PubMedCrossRefGoogle Scholar
  86. 86.
    Reid GE, Grim SA, Sankary H, Benedetti E, Oberholzer J, Clark NM. Early intra-abdominal infections associated with orthotopic liver transplantation. Transplantation. 2009;87(11):1706–11.PubMedCrossRefGoogle Scholar
  87. 87.
    Avkan-Oguz V, Unek T, Firuzan E, Ozbilgin M, Egeli T, Bacakoglu A, et al. Bacterial pathogens isolated in liver transplant recipients with surgical site infection and antibiotic treatment. Transplant Proc. 2015;47(5):1495–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Shields RK, Clancy CJ, Minces LR, Kwak EJ, Silveira FP, Abdel Massih RC, et al. Staphylococcus aureus infections in the early period after lung transplantation: epidemiology, risk factors, and outcomes. J Heart Lung Transplant. 2012;31(11):1199–206.PubMedCrossRefGoogle Scholar
  89. 89.
    Aguilar-Guisado M, Givalda J, Ussetti P, Ramos A, Morales P, Blanes M, et al. Pneumonia after lung transplantation in the RESITRA Cohort: a multicenter prospective study. Am J Transplant. 2007;7(8):1989–96.PubMedCrossRefGoogle Scholar
  90. 90.
    Montoya JG, Giraldo LF, Efron B, Stinson EB, Gamberg P, Hunt S, et al. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 2001;33(5):629–40.PubMedCrossRefGoogle Scholar
  91. 91.
    Vidal E, Torre-Cisneros J, Blanes M, Montejo M, Cervera C, Aguado JM, et al. Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort. Transpl Infect Dis. 2012;14(6):595–603.PubMedCrossRefGoogle Scholar
  92. 92.
    Lyerova L, Viklicky O, Nemcova D, Teplan V. The incidence of infectious diseases after renal transplantation: a single-centre experience. Int J Antimicrob Agents. 2008;31 Suppl 1:S58–62.PubMedCrossRefGoogle Scholar
  93. 93.
    Maraha B, Bonten H, van Hooff H, Fiolet H, Buiting AG, Stobberingh EE. Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect. 2001;7(11):619–25.PubMedCrossRefGoogle Scholar
  94. 94.
    Lopez-Medrano F, Garcia-Bravo M, Morales JM, Andres A, San Juan R, Lizasoain M, et al. Urinary tract infection due to Corynebacterium urealyticum in kidney transplant recipients: an underdiagnosed etiology for obstructive uropathy and graft dysfunction-results of a prospective cohort study. Clin Infect Dis. 2008;46(6):825–30.PubMedCrossRefGoogle Scholar
  95. 95.
    Justo JA, Bookstaver PB. Antibiotic lock therapy: review of technique and logistical challenges. Infect Drug Resist. 2014;7:343–63.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Raad I, Chaftari AM. Advances in prevention and management of central line-associated bloodstream infections in patients with cancer. Clin Infect Dis. 2014;59 Suppl 5:S340–3.PubMedCrossRefGoogle Scholar
  97. 97.
    van der Lelie H, Leverstein-Van Hall M, Mertens M, van Zaanen HC, van Oers RH, Thomas BL, et al. Corynebacterium CDC group JK (Corynebacterium jeikeium) sepsis in haematological patients: a report of three cases and a systematic literature review. Scand J Infect Dis. 1995;27(6):581–4.PubMedCrossRefGoogle Scholar
  98. 98.
    Rozdzinski E, Kern W, Schmeiser T, Kurrle E. Corynebacterium jeikeium bacteremia at a tertiary care center. Infection. 1991;19(4):201–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Soriano F, Zapardiel J, Nieto E. Antimicrobial susceptibilities of Corynebacterium species and other non-spore-forming Gram-positive bacilli to 18 antimicrobial agents. Antimicrob Agents Chemother. 1995;39(1):208–14.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Wang CC, Mattson D, Wald A. Corynebacterium jeikeium bacteremia in bone marrow transplant patients with Hickman catheters. Bone Marrow Transplant. 2001;27(4):445–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Schoen C, Unzicker C, Stuhler G, Elias J, Einsele H, Grigoleit GU, et al. Life-threatening infection caused by daptomycin-resistant Corynebacterium jeikeium in a neutropenic patient. J Clin Microbiol. 2009;47(7):2328–31.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Chavan RS, Pannaraj PS, Luna RA, Szabo S, Adesina A, Versalovic J, et al. Significant morbidity and mortality attributable to rothia mucilaginosa infections in children with hematological malignancies or following hematopoietic stem cell transplantation. Pediatr Hematol Oncol. 2013;30(5):445–54.PubMedCrossRefGoogle Scholar
  103. 103.
    Lee AB, Harker-Murray P, Ferrieri P, Schleiss MR, Tolar J. Bacterial meningitis from Rothia mucilaginosa in patients with malignancy or undergoing hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2008;50(3):673–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Boyle NM, Podczervinski S, Jordan K, Stednick Z, Butler-Wu S, McMillen K, et al. Bacterial foodborne infections after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20(11):1856–61.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Safdar A, Papadopoulous EB, Armstrong D. Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection. Bone Marrow Transplant. 2002;29(11):913–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Lebeaux D, Morelon E, Suarez F, Lanternier F, Scemla A, Frange P, et al. Nocardiosis in transplant recipients. Eur J Clin Microbiol Infect Dis. 2014;33(5):689–702.PubMedCrossRefGoogle Scholar
  107. 107.
    Rubin M, Hathorn JW, Marshall D, Gress J, Steinberg SM, Pizzo PA. Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia. Ann Intern Med. 1988;108(1):30–5.PubMedCrossRefGoogle Scholar
  108. 108.
    Feld R. Vancomycin as part of initial empirical antibiotic therapy for febrile neutropenia in patients with cancer: pros and cons. Clin Infect Dis. 1999;29(3):503–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Paul M, Borok S, Fraser A, Vidal L, Leibovici L. Empirical antibiotics against Gram-positive infections for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2005;55(4):436–44.PubMedCrossRefGoogle Scholar
  110. 110.
    Marron A, Carratala J, Gonzalez-Barca E, Fernandez-Sevilla A, Alcaide F, Gudiol F. Serious complications of bacteremia caused by Viridans streptococci in neutropenic patients with cancer. Clin Infect Dis. 2000;31(5):1126–30.PubMedCrossRefGoogle Scholar
  111. 111.
    European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group. Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. J Infect Dis. 1991;163(5):951–8.CrossRefGoogle Scholar
  112. 112.
    Erjavec Z, de Vries-Hospers HG, Laseur M, et al. A prospective, randomized, double-blinded, placebo-controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy. J Antimicrob Chemother. 2000;45:843–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Cometta A, Kern WV, De Bock R,et al. Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy. Clin Infect Dis. 2003;37:382–9.Google Scholar
  114. 114.
    Vardakas KZ, Samonis G, Chrysanthopoulou SA, Bliziotis IA, Falagas ME. Role of glycopeptides as part of initial empirical treatment of febrile neutropenic patients: a meta-analysis of randomised controlled trials. Lancet Infect Dis. 2005;5(7):431–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826–35.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    National Comprehensive Cancer Network (NCCN). Prevention and treatment of cancer-related infections V 2.2015. Accessed July 5.
  117. 117.
    Tam CS, O'Reilly M, Andresen D, Lingaratnam S, Kelly A, Burbury K, et al. Use of empiric antimicrobial therapy in neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee. Intern Med J. 2011;41(1b):90–101.PubMedCrossRefGoogle Scholar
  118. 118.
    Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012;30(35):4427–38.PubMedCrossRefGoogle Scholar
  119. 119.
    Rybak JM, Barber KE, Rybak MJ. Current and prospective treatments for multidrug-resistant Gram-positive infections. Expert Opin Pharmacother. 2013;14(14):1919–32.PubMedCrossRefGoogle Scholar
  120. 120.
    Ager S, Gould K. Clinical update on linezolid in the treatment of Gram-positive bacterial infections. Infect Drug Resist. 2012;5:87–102.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Kalil AC, Van Schooneveld TC, Fey PD, Rupp ME. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis. JAMA. 2014;312(15):1552–64.PubMedCrossRefGoogle Scholar
  122. 122.
    Soriano A, Marco F, Martinez JA, Pisos E, Almela M, Dimova VP, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46(2):193–200.PubMedCrossRefGoogle Scholar
  123. 123.
    Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, et al. Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations. J Infect Dis. 2011;204(3):340–7.PubMedCrossRefGoogle Scholar
  124. 124.
    van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012;54(6):755–71.PubMedCrossRefGoogle Scholar
  125. 125.
    Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis. 2011;52(8):975–81.PubMedCrossRefGoogle Scholar
  126. 126.
    Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP. Vancomycin: we can’t get there from here. Clin Infect Dis. 2011;52(8):969–74.PubMedCrossRefGoogle Scholar
  127. 127.
    Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents. 2011;37(2):95–101.PubMedCrossRefGoogle Scholar
  128. 128.
    Walraven CJ, North MS, Marr-Lyon L, Deming P, Sakoulas G, Mercier RC. Site of infection rather than vancomycin MIC predicts vancomycin treatment failure in methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2011;66(10):2386–92.PubMedCrossRefGoogle Scholar
  129. 129.
    Chang FY, Peacock Jr JE, Musher DM, Triplett P, MacDonald BB, Mylotte JM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine. 2003;82(5):333–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Gould IM, Miro JM, Rybak MJ. Daptomycin: the role of high-dose and combination therapy for Gram-positive infections. Int J Antimicrob Agents. 2013;42(3):202–10.PubMedCrossRefGoogle Scholar
  131. 131.
    Gonzalez-Ruiz A, Gargalianos-Kakolyris P, Timerman A, Sarma J, Jose Gonzalez Ramallo V, Bouylout K, et al. Daptomycin in the clinical setting: 8-year experience with Gram-positive bacterial infections from the EU-CORE(SM) registry. Adv Ther. 2015;32(6):496–509.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Rolston KV, Besece D, Lamp KC, Yoon M, McConnell SA, White P. Daptomycin use in neutropenic patients with documented Gram-positive infections. Support Care Cancer. 2014;22(1):7–14.PubMedCrossRefGoogle Scholar
  133. 133.
    Hall AD, Steed ME, Arias CA, Murray BE, Rybak MJ. Evaluation of standard- and high-dose daptomycin versus linezolid against vancomycin-resistant Enterococcus isolates in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother. 2012;56(6):3174–80.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    McKinnell JA, Arias CA. Linezolid vs daptomycin for vancomycin-resistant enterococci: the evidence gap between trials and clinical experience. Clin Infect Dis. 2015;61(6):879–82.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Woytowish MR, Maynor LM. Clinical relevance of linezolid-associated serotonin toxicity. Ann Pharmacother. 2013;47(3):388–97.PubMedCrossRefGoogle Scholar
  136. 136.
    Jaksic B, Martinelli G, Perez-Oteyza J, Hartman CS, Leonard LB, Tack KJ. Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer. Clin Infect Dis. 2006;42(5):597–607.PubMedCrossRefGoogle Scholar
  137. 137.
    Cohen N, Mihu CN, Seo SK, Chung D, Chou J, Heller G, et al. Hematologic safety profile of linezolid in the early periengraftment period after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15(10):1337–41.PubMedCrossRefGoogle Scholar
  138. 138.
    Radunz S, Juntermanns B, Kaiser GM, Treckmann J, Mathe Z, Paul A, et al. Efficacy and safety of linezolid in liver transplant patients. Transpl Infect Dis. 2011;13(4):353–8.PubMedCrossRefGoogle Scholar
  139. 139.
    Mendes RE, Deshpande LM, Jones RN. Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat. 2014;17(1–2):1–12.PubMedCrossRefGoogle Scholar
  140. 140.
    Peeters MJ, Sarria JC. Clinical characteristics of linezolid-resistant Staphylococcus aureus infections. Am J Med Sci. 2005;330(2):102–4.PubMedCrossRefGoogle Scholar
  141. 141.
    Pogue JM, Paterson DL, Pasculle AW, Potoski BA. Determination of risk factors associated with isolation of linezolid-resistant strains of vancomycin-resistant Enterococcus. Infect Control Hosp Epidemiol. 2007;28(12):1382–8.PubMedCrossRefGoogle Scholar
  142. 142.
    Dobbs TE, Patel M, Waites KB, Moser SA, Stamm AM, Hoesley CJ. Nosocomial spread of Enterococcus faecium resistant to vancomycin and linezolid in a tertiary care medical center. J Clin Microbiol. 2006;44(9):3368–70.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Burdette SD, Trotman R. Tedizolid: the first once daily oxazolidinone class antibiotic. Clin Infect Dis. 2015;61(8):1315–21.PubMedCrossRefGoogle Scholar
  144. 144.
    Yahav D, Lador A, Paul M, Leibovici L. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother. 2011;66(9):1963–71.PubMedCrossRefGoogle Scholar
  145. 145.
    Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis. 2011;11(11):834–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Open Access This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Division of Infectious Diseases, IRCCS San Martino Hospital – IST, Department of Health Sciences (DISSAL)University of GenovaGenoaItaly

Personalised recommendations