Skip to main content
Log in

Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Bacteremia remains a major cause of life-threatening complication in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture have been reported in cancer patients over the past years. The aim of our systematic review was to inventory the recent trends in epidemiology and antibiotic resistance of microorganisms causing bacteremia in cancer patients. Data for this review was identified by searches of Medline, Scopus and Cochrane Library for indexed articles and abstracts published in English since 2008. The principal search terms were: “antimicrobial resistance”, “bacteremia”, “bacterial epidemiology”, “bloodstream infection”, “cancer patients”, “carbapenem resistance”, “Escherichia coli resistance”, “extended-spectrum β-lactamase producing E. coli”, “febrile neutropenia”, “fluoroquinolone resistance”, “neutropenic cancer patient”, “vancomycin-resistant Enterococcus”, and “multidrug resistance”. Boolean operators (NOT, AND, OR) were also used in succession to narrow and widen the search. Altogether, 27 articles were selected to be analyzed in the review. We found that Gram-negative bacteria were the most frequent pathogen isolated, particularly in studies with minimal use of antibiotic prophylaxis. Another important trend is the extensive emergence of antimicrobial-resistant strains associated with increased risk of morbidity, mortality and cost. This increasing incidence of antibiotic resistance has been reported in Gram-negative bacteria as well as in Gram-positive bacteria. This exhaustive review, reporting the recent findings in epidemiology and antibiotic resistance of bacteremia in cancer patients, highlights the necessity of local continuous surveillance of bacteremia and stringent enforcement of antibiotic stewardship programs in cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Klastersky J (2004) Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis 39:S327

    Article  Google Scholar 

  2. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR, Infectious Diseases Society of America (2011) 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 52(4):427–431

    Article  PubMed  Google Scholar 

  3. Arnold RJ, Gabrail N, Rat M, Kim R, Sung JC, Zhou Y (2005) Clinical implications of chemotherapy induced diarrhea in patients with cancer. J Support Oncol 3:227–232

    PubMed  Google Scholar 

  4. van Vliet MJ, Harmsen HJ, de Bont ES, Tissing WJ (2010) The role of intestinal microbiota in the development and severity of chemotherapy-induced Mucositis. Plos Pathol 27:e1000879

    Article  Google Scholar 

  5. Jones RN (1999) Contemporary antimicrobial susceptibility pattern of bacterial pathogens commonly associated with febrile patients with neutropenia. Clin Infect Dis 29:495–502

    Article  CAS  PubMed  Google Scholar 

  6. Irfan S, Idrees F, Mehraj V, Habib F, Adil S, Hasan R (2008) Emergence of Carbapenem resistant Gram negative and vancomycin resistant Gram positive organisms in bacteremic isolates of febrile neutropenic patients: a descriptive study. BMC Infect Dis 8:80

    Article  PubMed  Google Scholar 

  7. Ramphal R (2004) Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens. Clin Infect Dis 39:S25–S31

    Article  PubMed  Google Scholar 

  8. Zinner SH (1999) Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria. Clin Infect Dis 29:490–494

    Article  CAS  PubMed  Google Scholar 

  9. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB (2003) 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 36:1103–1110

    Article  PubMed  Google Scholar 

  10. Sharma A, Lokeshwar N (2005) Febrile neutropenia in haematological malignancies. J Postgrad Med 51:42–48

    Google Scholar 

  11. Wu HS, Kuo SC, Lee YT, Yang YS, Cheng SS, Chen TL, Fung CP (2012) Clinical characteristics and prognostic factors of Acinetobacter nosocomialis bacteraemia in patients with solid tumours. Clin Microbiol Infect 18(9):E373–E376

    Article  PubMed  Google Scholar 

  12. Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, Oh MD, Choe KW (2004) Bloodstream infections due to extended spectrum factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy. Antimicrob Agents Chemother 48:4574–4581

    Article  CAS  PubMed  Google Scholar 

  13. Kim YK, Pai H, Lee HJ, Park SE, Choi EH, Kim J, Kim JH, Kim EC (2002) Bloodstream infections by extended-spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother 46(1481):1491

    Google Scholar 

  14. Cattaneo C, Antoniazzi F, Casari S, Ravizzola G, Gelmi M, Pagani C, D’Adda M, Morello E, Re A, Borlenghi E, Manca N, Rossi G (2012) P. aeruginosa bloodstream infections among hematological patients: an old or new question? Ann Hematol 91(8):1299–1304

    Article  PubMed  Google Scholar 

  15. Kjellander C, Björkholm M, Cherif H, Kalin M, Giske CG (2012) 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 88(5):422–430

    Article  CAS  PubMed  Google Scholar 

  16. Chong Y, Yakushiji H, Ito Y, Kamimura T (2011) Clinical impact of fluoroquinolone prophylaxis in neutropenic patients with hematological malignancies. Int J Infect Dis 15(4):e277–e281

    Article  CAS  PubMed  Google Scholar 

  17. Saghir S, Faiz M, Saleem M, Younus A, Aziz H (2009) Characterization and anti-microbial susceptibility of Gram-negative bacteria isolated from bloodstream infections of cancer patients on chemotherapy in Pakistan. Indian J Med 27:341–347

    CAS  Google Scholar 

  18. Kang CI, Song JH, Chung DR, Peck KR, Yeom JS, Son JS, Wi YM, on behalf of the Korean Network for Study on Infectious Diseases (KONSID) (2012) Bloodstream infections in adult patients with cancer: clinical features and pathogenic significance of Staphylococcus aureus bacteremia. Support Care Cancer 20(10):2371–2378

    Google Scholar 

  19. Lanoix JP, Pluquet E, Lescure FX, Bentayeb H, Lecuyer E, Boutemy M, Dumont P, Jounieaux V, Schmit JL, Dayen C, Douadi Y (2011) Bacterial infection profiles in lung cancer patients with febrile neutropenia. BMC Infect Dis 11:183

    Article  PubMed  Google Scholar 

  20. Gudiol C, Bodro M, Simonetti A, Tubau F, González-Barca E, Cisnal M, Domingo-Domenech E, Jiménez L, Carratalà J (2012) Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect. doi:10.1111/j.1469-0691.2012.03879

  21. Trecarichi EM, Tumbarello M, Spanu T, Caira M, Fianchi L, Chiusolo P, Fadda G, Leone G, Cauda R, Pagano L (2009) Incidence and clinical impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies. J Infect 58(4):299–307

    Article  PubMed  Google Scholar 

  22. Bhusal Y, Mihu CN, Tarrand JJ, Rolston KV (2011) Incidence of fluoroquinolone-resistant and extended-spectrum β-lactamase-producing Escherichia coli at a comprehensive cancer center in the United States. Chemotherapy 57(4):335–338

    Article  CAS  PubMed  Google Scholar 

  23. Jacobson K, Rolston K, Elting L, LeBlanc B, Whimbey E, Ho DH (1999) Susceptibility surveillance among Gram-negative bacilli at a cancer center. Chemotherapy 45:325–334

    Article  CAS  PubMed  Google Scholar 

  24. Mihu CN, Rhomberg PR, Jones RN, Coyle E, Prince RA, Rolston KV (2010) Escherichia coli resistance to quinolones at a comprehensive cancer center. Diagn Microbiol Infect Dis 67(3):266–269

    Article  CAS  PubMed  Google Scholar 

  25. Bell JM, Turnidge JD, Gales AC, Pfaller MA, Jones RN, Sentry APAC Study Group (2002) Prevalence of extended-spectrum beta-lactamase (ESBL)—producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998–99). Diagn Microbiol Infect Dis 42:193–198

    Article  PubMed  Google Scholar 

  26. Gulay Z, Thomson CJ, Yulug N, Amyes SG (2000) High prevalence of extended spectrum beta-lactamase production among Klebsiella pneumoniae strains isolated at a university hospital in Turkey. J Chemother 12:145–152

    CAS  PubMed  Google Scholar 

  27. Vahaboglu H, Ozturk R, Aygun G, Coşkunkan F, Yaman A, Kaygusuz A, Leblebicioglu H, Balik I, Aydin K, Otkun M (1997) Widespread detection of PER-1–type extended-spectrum beta-lactamases among nosocomial Acinetobacter and Pseudomonas aeruginosa isolates in Turkey: a nationwide multicenter study. Antimicrob Agents Chemother 41:2265–2269

    CAS  PubMed  Google Scholar 

  28. Arnan M, Gudiol C, Calatayud L, Liñares J, Dominguez MA, Batlle M, Ribera JM, Carratalà J, Gudiol F (2011) Risk factors for, and clinical relevance of, faecal extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies. Eur J Clin Microbiol Infect Dis 30(3):355–360

    Article  CAS  PubMed  Google Scholar 

  29. Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, Arnan M, Marin M, Carratalà J, Gudiol F (2010) Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother 65(2):333–341

    Article  CAS  PubMed  Google Scholar 

  30. Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fätkenheuer G, Wisplinghoff H, Seifert H, Vehreschild MJ (2012) Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection 40(6):613–619

    Article  CAS  PubMed  Google Scholar 

  31. Kang CI, Chung DR, Ko KS, Peck KR, Song JH, Korean Network for Study of Infectious Diseases (2012) Risk factors for infection and treatment outcome of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in patients with hematologic malignancy. Ann Hematol 91(1):115–121

    Article  CAS  PubMed  Google Scholar 

  32. Almyroudis NG, Fuller A, Jakubowski A, Sepkowitz K, Jaffe D, Small TN, Kiehn TE, Pamer E, Papanicolaou GA (2005) Pre- and postengraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 7:11–17

    Article  CAS  PubMed  Google Scholar 

  33. Avery R, Kalaycio M, Pohlman B, Sobecks R, Kuczkowski E, Andresen S, Mossad S, Shamp J, Curtis J, Kosar J, Sands K, Serafin M, Bolwell B (2005) Early vancomycin resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course. Bone Marrow Transplant 35:497–499

    Article  CAS  PubMed  Google Scholar 

  34. Kapur D, Dorsky D, Feingold JM, Bona RD, Edwards RL, Aslanzadeh J, Tutschka PJ, Bilgrami S (2000) Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 25:147–152

    Article  CAS  PubMed  Google Scholar 

  35. Weinstock DM, Conlon M, Iovino C, Aubrey T, Gudiol C, Riedel E, Young JW, Kiehn TE, Zuccotti G (2007) Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant 13:615–621

    Article  PubMed  Google Scholar 

  36. Zirakzadeh A, Gastineau DA, Mandrekar JN, Burke JP, Johnston BP, Patel R (2008) Vancomycin-resistant enterococcal colonization appears associated with increased mortality among allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 41:385–392

    Article  CAS  PubMed  Google Scholar 

  37. Kamboj M, Chung D, Seo SK, Pamer EG, Sepkowitz KA, Jakubowski AA, Papanicolaou G (2010) The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transplant 16(11):1576–1581

    Article  PubMed  Google Scholar 

  38. Bossaer JB, Hall PD, Garrett-Mayer E (2010) Incidence of vancomycin-resistant enterococci (VRE) infection in high-risk febrile neutropenic patients colonized with VRE. Support Care Cancer 19(2):231–237

    Article  PubMed  Google Scholar 

  39. Quilty S, Kwok G, Hajkowicz K, Currie B (2009) High incidence of methicillin resistant Staphylococcus aureus sepsis and death in patients with febrile neutropenia at Royal Darwin Hospital. Intern Med J 39:557–559

    Article  CAS  PubMed  Google Scholar 

  40. Prabhash K, Medhekar A, Ghadyalpatil N, Noronha V, Biswas S, Kurkure P, Nair R, Kelkar R (2010) Blood stream infections in cancer patients: a single center experience of isolates and sensitivity pattern. Indian J Cancer 47:184–188

    Article  CAS  PubMed  Google Scholar 

  41. Karim M, Khan W, Farooqi B, Malik I (1991) Bacterial isolates in neutropenic febrile patients. J Pak Med Assoc 48:364–367

    Google Scholar 

  42. Rangaraj G, Granwehr BP, Jiang Y, Hachem R, Raad I (2010) Perils of quinolone exposure in cancer patients: breakthrough bacteremia with multidrug-resistant organisms. Cancer 116(4):967–973

    Article  PubMed  Google Scholar 

  43. Gudiol C, Tubau F, Calatayud L, Garcia-Vidal C, Cisnal M, Sánchez-Ortega I, Duarte R, Calvo M, Carratalà J (2011) Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother 66(3):657–663

    Article  CAS  PubMed  Google Scholar 

  44. Trecarichi EM, Tumbarello M, Caira M, Candoni A, Cattaneo C, Pastore D, Fanci R, Nosari A, Vianelli N, Busca A, Spadea A, Pagano L (2011) Multidrug resistant Pseudomonas aeruginosa bloodstream infection in adult patients with hematologic malignancies. Haematologica 96(1):e1–e3

    Article  PubMed  Google Scholar 

  45. Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Paesmans M (2007) Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents S1:S51–S59

    Article  Google Scholar 

  46. Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, Concia E (1996) Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis 23:795–805

    Article  CAS  PubMed  Google Scholar 

  47. Bow EJ (2011) Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis 24(6):545–553

    Article  CAS  PubMed  Google Scholar 

  48. CLSI (2008) Performance standards for antimicrobial susceptibility testing; eighteenth informational supplement. CLSI document M100-S18. Enterobacteriaceae M7MIC. Clinical and Laboratory Standards Institute, Wayne, PA, pp 98–101

  49. Saito T, Yoshioka S, Iinuma Y, Takakura S, Fujihara N, Ichinohe T, Ishikawa T, Uchiyama T, Ichiyama S (2008) Effects on spectrum and susceptibility patterns of isolates causing bloodstream infection by restriction of fluoroquinolone prophylaxis in a hematology–oncology unit. Eur J Clin Microbiol Infect Dis 27:209–216

    Article  CAS  PubMed  Google Scholar 

  50. Engels EA, Ellis CA, Supran SE, Schmid CH, Barza M, Schenkein DP, Koc Y, Miller KB, Wong JB (1999) Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk. Clin Infect Dis 28:256–266

    Article  CAS  PubMed  Google Scholar 

  51. Ghosh I, Raina V, Kumar L, Sharma A, Bakhshi S, Thulkar S, Kapil A (2012) Profile of infections and outcome in high-risk febrile neutropenia: experience from a tertiary care cancer center in India. Med Oncol 29(2):1354–1360

    Article  PubMed  Google Scholar 

  52. Richard P, Delangi MH, Raffi F, Espaze E, Richet H (2001) Impact of fluoroquinolone administration on the emergence of fluoroquinolone-resistant, gram-negative bacilli from gastrointestinal flora. Clin Infect Dis 32:162–166

    Article  CAS  PubMed  Google Scholar 

  53. Cheong HJ, Yoo CW, Sohn JW, Kim WJ, Kim MJ, Park SC (2001) Bacteremia due to quinolone-resistant Escherichia coli in a teaching hospital in South Korea. Clin Infect Dis 33:48–53

    Article  CAS  PubMed  Google Scholar 

  54. McDonald LC, Chen FJ, Lo HJ, Yin HC, Lu PL, Huang CH, Chen P, Lauderdale TL, Ho M (2001) Emergence of reduced susceptibility and resistance to fluoroquinolones in Escherichia coli in Taiwan and contributions of distinct selective pressures. Antimicrob Agents Chemother 45:3084–3089

    Article  CAS  PubMed  Google Scholar 

  55. Lodise TP Jr, Patel N, Kwa A, Graves J, Furuno JP, Graffunder E, Lomaestro B, McGregor JC (2007) Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother 51(10):3510–3515

    Article  CAS  PubMed  Google Scholar 

  56. Giske CG, Monnet DL, Cars O, Carmeli Y, ReAct-Action on Antibiotic Resistance (2008) Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob Agents Chemother 52(3):813–821

    Article  CAS  PubMed  Google Scholar 

  57. Caselli D, Cesaro S, Ziino O, Zanazzo G, Manicone R, Livadiotti S, Cellini M, Frenos S, Milano GM, Cappelli B, Licciardello M, Beretta C, Aricò M, Castagnola E, Infection Study Group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) (2010) Multidrug resistant Pseudomonas aeruginosa infection in children undergoing chemotherapy and hematopoietic stem cell transplantation. Haematologica 95(9):1612–1615

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. Montassier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montassier, E., Batard, E., Gastinne, T. et al. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis 32, 841–850 (2013). https://doi.org/10.1007/s10096-013-1819-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-013-1819-7

Keywords

Navigation