Is current initial empirical antibiotherapy appropriate to treat bloodstream infections in short-duration chemo-induced febrile neutropenia?
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Fever of unknown origin is by far the most common diagnosis in low-risk febrile neutropenic patients undergoing chemotherapy. The current empirical regimen combines amoxicillin-clavulanic acid and fluoroquinolones in low-risk neutropenic patients. The aim of this study was to assess the appropriateness of antibiotherapy and the outcome of bloodstream infections (BSI) in patients with expected neutropenia of short duration.
This 2-year monocentric retrospective study included all consecutive neutropenic febrile adult patients with expected duration of neutropenia ≤ 7 days. They were classified into low- and high-risk groups for complications using the MASCC index. Appropriateness of initial empirical antibiotic regimen was assessed for each BSI. Multivariate analysis was performed to identify factors associated with mortality.
Over the study period, 189 febrile episodes with positive blood cultures in neutropenic patients were reported, of which 44 occurred during expected duration of neutropenia ≤ 7 days. Patients were classified as high-risk (n = 27) and low-risk (n = 17). Gram-negative bacteria BSI represented 57% of cases, including only two multidrug-resistant bacteria in high-risk patients. Initial empirical antibiotherapy was appropriate in 86% of cases, and inappropriate in the event of coagulase-negative Staphylococcus BSI (14%), although the outcome was always favorable. In low-risk patients, no deaths and only 12% of severe complications were reported, contrasting with mortality and complication rates of 48% (p < 0.001) and 63% in high-risk patients (p < 0.001), respectively.
Outcome of BSI is favorable in low-risk febrile neutropenic patients, even with inappropriate empirical initial antibiotic regimen for coagulase-negative Staphylococcus BSI. Initial in-hospital assessment and close monitoring of these patients are however mandatory.
KeywordsFebrile neutropenia Bloodstream infections Empirical antibiotic regimen
We thank Jeffrey Ashram for editing the manuscript.
Compliance with ethical standards
The National Data Protection Authority (Commission Nationale Informatique et Libertés), which is responsible for protection of individual data in France, approved the panel and its procedures.
Conflict of interest
AJ received travel grants for conferences from Pierre Fabre, Sanofi, Pfizer, and Ipsen.
BR received travel grants for conferences from Pfizer, Gilead, and Astellas, and speaker’s fees from Merck/MSD, Gilead, and Basilea.
AM received travel grants for conferences from MSD, EUMEDICA, and bioMérieux.
The other authors declared no conflict of interest.
- 4.Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, Gallagher J, Herrstedt J, Rapoport B, Rolston K, Talcott J (2000) The Multinational Association for Supportive Care in Cancer Risk Index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 18:3038–3051CrossRefGoogle Scholar
- 5.Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston AA, Marr KA, Rolston KV, Ramsey SD (2013) Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol Off J Am Soc Clin Oncol 31:794–810CrossRefGoogle Scholar
- 8.Cullen M, Steven N, Billingham L, Gaunt C, Hastings M, Simmonds P, Stuart N, Rea D, Bower M, Fernando I, Huddart R, Gollins S, Stanley A, Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/- Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group (2005) Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 353:988–998CrossRefGoogle Scholar
- 9.Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D'Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foà R, del Favero A, Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) Infection Program (2005) Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 353:977–987CrossRefGoogle Scholar
- 10.Kern WV, Cometta A, De Bock R, Langenaeken J, Paesmans M, Gaya H (1999) Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 341:312–318CrossRefGoogle Scholar
- 11.Innes HE, Smith DB, O’Reilly SM, Clark PI, Kelly V, Marshall E (2003) Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study. Br J Cancer 89:43–49CrossRefGoogle Scholar
- 12.Viscoli C, Cometta A, Kern WV et al (2006) Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 12:212–216Google Scholar
- 15.National Healthcare Safety Network bacteremia definiton. Available at: https://www.google.fr/search?ei=FfDeW6XKKoKXlwS9_IfQCw&q=national+healthcare+safety+network+bacteremia+definiton&oq=national+healthcare+safety+network+bacteremia+definiton. Accessed 17 Mar 2018
- 18.Magiorakos A-P, Srinivasan A, Carey RB et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 18:268–281Google Scholar
- 19.EUCAST: Breakpoints tables for interpretation of MICs and zone diameters Version 4.0, valid from 2014-31-12. Available at: http://www.eucast.org/ast_of_bacteria/previous_versions_of_documents/. Accessed 26 Dec 2018
- 20.Société Française de Microbiologie. Comité de l’antibiogramme de la Société Française de Microbiologie, Recommandations 2017. 2017; Available at: http://www.sfm-microbiologie.org/UserFiles/files/casfm/CASFMV1_0_MARS_2017.pdf. Accessed 27 Mar 2018
- 22.Kern WV, Marchetti O, Drgona L, Akan H, Aoun M, Akova M, de Bock R, Paesmans M, Viscoli C, Calandra T (2013) Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy--EORTC infectious diseases group trial XV. J Clin Oncol Off J Am Soc Clin Oncol 31:1149–1156CrossRefGoogle Scholar
- 24.Cornely OA, Wicke T, Seifert H, Bethe U, Schwonzen M, Reichert D, Ullmann AJ, Karthaus M, Breuer K, Salzberger B, Diehl V, Fätkenheuer G (2004) Once-daily oral levofloxacin monotherapy versus piperacillin/tazobactam three times a day: a randomized controlled multicenter trial in patients with febrile neutropenia. Int J Hematol 79:74–78CrossRefGoogle Scholar
- 26.Santos Sanches I, Mato R, de Lencastre H, Tomasz A, CEM/NET Collaborators and the International Collaborators. Patterns of multidrug resistance among methicillin-resistant hospital isolates of coagulase-positive and coagulase-negative staphylococci collected in the international multicenter study RESIST in 1997 and 1998. Microb Drug Resist Larchmt N 2000; 6:199–211Google Scholar
- 29.Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, Signorini L, Re A, Carosi G, Rossi G (2008) 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 61:721–728CrossRefGoogle Scholar
- 32.Lafaurie M, Porcher R, Donay J-L, Touratier S, Molina J-M (2012) Reduction of fluoroquinolone use is associated with a decrease in methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Pseudomonas aeruginosa isolation rates: a 10 year study. J Antimicrob Chemother 67:1010–1015CrossRefGoogle Scholar
- 38.Gudiol C, Bodro M, Simonetti A et al (2013) Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 19:474–479Google Scholar
- 39.Zhang S, Wang Q, Ling Y, Hu X (2015) Fluoroquinolone resistance in bacteremic and low risk febrile neutropenic patients with cancer. BMC Cancer 15 Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326398/
- 40.Todeschini G, Franchini M, Tecchio C et al (1998) Improved prognosis of Pseudomonas aeruginosa bacteremia in 127 consecutive neutropenic patients with hematologic malignancies. Int J Infect Dis IJID Off Publ Int Soc Infect Dis 3:99–104Google Scholar
- 45.European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe in 2014. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). 2015. Available at: https://www.google.fr/search?q=European+Centre+for+Disease+Prevention+and+Control.+Antimicrobial+resistance+surveillance+in+Europe+in+2014. Accessed 7 Apr 2018
- 46.Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO, American Society of Clinical Oncology (2015 Oct 1) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol 33(28):3199–3212. https://doi.org/10.1200/JCO.2015.62.3488 CrossRefPubMedGoogle Scholar