Advertisement

Bloodstream infection in patients with head and neck cancer: a major challenge in the cetuximab era

  • M. Marín
  • C. Gudiol
  • F. Castet
  • M. Oliva
  • I. Peiró
  • C. Royo-Cebrecos
  • J. Carratalà
  • R. Mesia
Research Article

Abstract

Purpose

To assess the impact of bloodstream infection (BSI) in patients with head and neck cancer (HNC) in the cetuximab era.

Methods

We prospectively analysed the epidemiology, microbiology and outcomes of 51 BSI episodes occurring in 48 patients with HNC (2006–2017). We performed a retrospective matched-cohort study (1:2) to determine the risk factors for BSI. Finally, we compared patients who died with those who survived to identify risk factors for mortality.

Results

The most frequent HNC localization was the oropharynx (43%), and pneumonia was the most frequent source (25%). Gram-positive BSI occurred in 55% cases, mainly due to Streptococcus pneumoniae (21%), and among Gram-negatives, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most frequent. Hypoalbuminemia (OR 8.4; 95% CI, 3.5–19.9), previous chemotherapy (OR, 3.2; 95% CI, 1.3–7.4) and cetuximab therapy (OR, 2.8; 95% CI, 1.6–6.7) were significant risk factors for BSI. Patients with BSI had a higher overall case-fatality rate than patients without BSI (OR, 4.4; 95% CI, 1.7–11.8). Hypoalbuminemia was an independent risk factor for the early (7 day) and overall (30 day) case-fatalities, with ORs of 0.8 (95% CI, 0.6–0.9) and 0.8 (95% CI, 0.7–0.97), respectively. The presence of comorbidities (OR, 7; 95% CI, 1.4–34) was also an independent risk factor for overall case-fatality.

Conclusions

BSI causes high mortality in patients with HNC and is most often secondary to pneumonia. It occurs mainly among patients with hypoalbuminemia who receive treatment with cetuximab or chemotherapy. The development of BSI in patients with HNC impairs their outcome, especially in the presence of hypoalbuminemia and comorbidities.

Keywords

Head and neck cancer Bloodstream infection Cetuximab Chemotherapy Hypoalbuminemia 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This observational study was approved by the Institutional Review Board Comité Ético de Investigación Clínica del Hospital Universitari de Bellvitge (Ethics Committee of Clinical Research-Hospital Universitari de Bellvitge). To protect personal privacy, identifying information of each patient in the electronic database was encrypted.

Informed consent

Informed consent was waived by the Clinical Research Ethics Committee because no intervention was involved and no patient identifying information was included.

References

  1. 1.
    Maños M, Giralt J, Rueda A, Cabrera J, Martinez-Trufero J, Marruecos J, et al. Multidisciplinary management of head and neck cancer: first expert consensus using Delphi methodology from the Spanish society for head and neck cancer (part 1). Oral Oncol. 2017.  https://doi.org/10.1016/j.oraloncology.2017.04.004.CrossRefPubMedGoogle Scholar
  2. 2.
    Rueda A, Giralt J, Maños M, Lozano A, Sistiaga A, Garcia-Miragall E, et al. Multidisciplinary management of head and neck cancer: first expert consensus using Delphi methodology from the Spanish society for head and neck cancer (part 2). Oral Oncol. 2017.  https://doi.org/10.1016/j.oraloncology.2017.04.005.CrossRefPubMedGoogle Scholar
  3. 3.
    Marur S, Forastiere AA. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91:386–96.  https://doi.org/10.1016/j.mayocp.2015.12.017.CrossRefPubMedGoogle Scholar
  4. 4.
    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, update by the infectious diseases society of America. Clin Infect Dis. 2010;2011:52.  https://doi.org/10.1093/cid/cir073.CrossRefGoogle Scholar
  5. 5.
    Klastersky J. Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis. 2004;39(Suppl 1):S32–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Montassier E, Batard E, Gastinne T, Potel G, De La Cochetière MF. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis. 2013;32:841–50.CrossRefPubMedGoogle Scholar
  7. 7.
    Gudiol C, Tubau F, Calatayud L, Garcia-Vidal C, Cisnal M, Sánchez-Ortega I, et al. Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother. 2011;66:657–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Anatoliotaki M, Valatas V, Mantadakis E, Apostolakou H, Mavroudis D, Georgoulias V, et al. Bloodstream infections in patients with solid tumors: associated factors, microbial spectrum and outcome. Infection. 2004;32:65–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Schelenz S, Nwaka D, Hunter PR. Longitudinal surveillance of bacteraemia in haematology and oncology patients at a UK cancer centre and the impact of ciprofloxacin use on antimicrobial resistance. J Antimicrob Chemother. 2013;68:1431–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.CrossRefPubMedGoogle Scholar
  11. 11.
    Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.CrossRefPubMedGoogle Scholar
  12. 12.
    Lee CC, Ho HC, Hsiao SH, Huang TT, Lin HY, Li SC, et al. Infectious complications in head and neck cancer patients treated with cetuximab: propensity score and instrumental variable analysis. PLoS One. 2012;7:e50163.  https://doi.org/10.1371/journal.pone.0050163.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Funakoshi T, Suzuki M, Tamura K. Infectious complications in cancer patients treated with anti-EGFR monoclonal antibodies cetuximab and panitumumab: a systematic review and meta-analysis. Cancer Treat Rev. 2014;40:1221–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Berardi R, Rinaldi S, Santini D, Vincenzi B, Giampieri R, Maccaroni E, et al. Increased rates of local complication of central venous catheters in the targeted anticancer therapy era: a 2-year retrospective analysis. Support Care Cancer. 2015;23:1295–302.CrossRefPubMedGoogle Scholar
  15. 15.
    Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51.CrossRefPubMedGoogle Scholar
  16. 16.
    Friedman ND, Kaye KS, Stout JE, McGarry S, et al. Health care-associated bloodstream infections in adults : a reason to change the accepted definiti. Ann Intern Med. 2002;137:791–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Basch E, Reeve B, Cleeland C, Sloan J, Schrag D, Atkinson TM, et al. Development of the patient-reported version of the common terminology criteria for adverse events (pro-CTCAE). Value Heal. 2010;13:A274–5.CrossRefGoogle Scholar
  18. 18.
    RS M. Sepsis, severe sepsis, and septic shock. 2010. https://doi.org/10.1016/b978-0-443-06839-3.00070-9.Google Scholar
  19. 19.
    CLSI. Performance standards for antimicrobial susceptibility testing. CLSI supplement M100S. 2016.Google Scholar
  20. 20.
    Falagas ME, Koletsi PK, Bliziotis IA. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J Med Microbiol. 2006;55:1619–29.CrossRefPubMedGoogle Scholar
  21. 21.
    EUCAST. Breakpoint tables for interpretation of MICs and zone diameters European Committee on antimicrobial susceptibility testing breakpoint tables for interpretation of MICs and zone diameters. EUCAST 2016:35–44.Google Scholar
  22. 22.
    Hosmer DW, Lemeshow S SR. Applied logistic regression, 3rd edition. 2013.  https://doi.org/10.1002/9781118548387.
  23. 23.
    Marín M, Gudiol C, Garcia-Vidal C, Ardanuy C, Carratalà J. Bloodstream infections in patients with solid tumors. Med Baltim. 2014;93:143–9.CrossRefGoogle Scholar
  24. 24.
    Viasus D, Garcia-Vidal C, Simonetti A, Manresa F, Dorca J, Gudiol F, et al. Prognostic value of serum albumin levels in hospitalized adults with community-acquired pneumonia. J Infect. 2013;66:415–23.CrossRefPubMedGoogle Scholar
  25. 25.
    Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis*. Crit Care Med. 2011;39:386–91.CrossRefPubMedGoogle Scholar
  26. 26.
    Artigas A, Wernerman J, Arroyo V, Vincent JL, Levy M. Role of albumin in diseases associated with severe systemic inflammation: pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care. 2016;33:62–70.CrossRefPubMedGoogle Scholar
  27. 27.
    Rodríguez-Baño J, Picón E, Gijón P, Hernández JR, Ruíz M, Peña C, et al. Community-onset bacteremia due to extended-spectrum β-lactamase–producing Escherichia coli: risk factors and prognosis. Clin Infect Dis. 2010;50:40–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Raad I, Hachem R, Hanna H, Bahna P, Chatzinikolaou I, Fang X, et al. Sources and outcome of bloodstream infections in cancer patients: the role of central venous catheters. Eur J Clin Microbiol Infect Dis. 2007;26:549–56.CrossRefPubMedGoogle Scholar
  29. 29.
    Marin M, Gudiol C, Ardanuy C, Garcia-Vidal C, Jimenez L, Domingo-Domenech E, et al. Factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection. Clin Microbiol Infect. 2015;21:583–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, et al. Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007;30:51–9.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of Medical OncologyCatalan Institute of Oncology (ICO), L’HospitaletBarcelonaSpain
  2. 2.Department of Infectious DiseasesHospital Universitari de BellvitgeBarcelonaSpain
  3. 3.IDIBELL (Institut d’Investigació Biomèdica de Bellvitge)L’HospitaletBarcelonaSpain
  4. 4.REIPI (Spanish Network for Research in Infectious Diseases)BarcelonaSpain
  5. 5.Department of MedicineUniversity of BarcelonaBarcelonaSpain
  6. 6.Clinical Nutrition UnitCatalan Institute of Oncology (ICO), L’HospitaletBarcelonaSpain

Personalised recommendations