Medical Oncology

, Volume 29, Issue 2, pp 1354–1360 | Cite as

Profile of infections and outcome in high-risk febrile neutropenia: experience from a tertiary care cancer center in India

  • Indranil Ghosh
  • Vinod Raina
  • Lalit Kumar
  • Atul Sharma
  • Sameer Bakhshi
  • Sanjay Thulkar
  • Arti Kapil
Original Paper


Objective of the present study was to describe the profile of infections in febrile neutropenia (FN) in acute leukemia and hematopoietic stem cell transplant (HSCT) with emphasis on response to therapy and outcome. In a prospective, observational single-institutional study, consecutive episodes of high-risk FN were enrolled over a 1½-year period. Uniform antibiotic policy and response criteria were used. Of the 200 episodes enrolled, acute leukemia induction comprised 40.5%, consolidation with high-dose cytarabine 22.5%, HSCT 29% (auto-HSCT 84%), and others 8% of the episodes, respectively. Microbiologically documented infections comprised 30% episodes, while bacteremia was documented in 26% episodes. Gram-negative isolates were more common (55.7%). Cefoperazone–sulbactam had the highest in vitro efficacy against Gram-negative rods. Carbapenem resistance was most prevalent among Acinetobacter spp. (80%) and Pseudomonas aeruginosa (50%). All Gram-positive cocci other than enterococci were susceptible to vancomycin, while 2/8 enterococci were resistant to it. Cefoperazone–sulbactam and amikacin were used as first-line antibiotics. Overall mortality was 8%. On multivariate analysis, mortality was associated with a nadir leukocyte count < 200/μl and an abnormal chest radiograph. Among high-risk FN patients, inspite of a high-level of resistance to antibiotics, a frontline regime containing cefoperazone–sulbactam could restrict the use of imipenem and resulted in an acceptable mortality of 8%.


Fever Neutropenia Acute leukemia Cefoperazone–sulbactam Microbial drug resistance Mortality 


Conflicts of interest



  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.
    Klastersky J, et al. Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007;30:S51–9.PubMedCrossRefGoogle Scholar
  3. 3.
    De Bock R, et al. Incidence of single agent Gram-negative bacteremias (SAGNB) in neutropenic cancer patients (NCP) in EORTC-IATG trials of empirical therapy for febrile neutropenia [abstract L-773]. In: Program and abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (Chicago). Washington, DC: American Society for Microbiology, 2001:445.Google Scholar
  4. 4.
    Kanafani ZA, et al. Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade. Int J Infect Dis. 2007;11:450–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Baskaran ND, Gan GG, Adeeba K, Sam IC. Bacteremia in patients with febrile neutropenia after chemotherapy at a university medical center in Malaysia. Int J Infect Dis. 2007;6:513–7.CrossRefGoogle Scholar
  6. 6.
    Hughes WT, et al. 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34:730–51.PubMedCrossRefGoogle Scholar
  7. 7.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prevention and treatment of cancer-related infections (v2.2009). Available online at (Accessed 16 Decemeber 2010).
  8. 8.
    Mathur P, Chaudhry R, Kumar L, Kapil A, Dhawan B. A study of bacteremia in febrile neutropenic patients at a tertiary-care hospital with special reference to anaerobes. Med Oncol. 2002;19:267–72.PubMedCrossRefGoogle Scholar
  9. 9.
    Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia: an analysis of 222 febrile neutropenic episodes. Pediatr Hematol Oncol. 2008;25:385–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Gupta A, et al. Infections in acute myeloid leukemia: an analysis of 382 febrile episodes. Med Oncol. 2010;27:1037–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Prabhash K, et al. Blood stream infections in cancer patients: a single center experience of isolates and sensitivity pattern. Indian J Cancer. 2010;47:184–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Klastersky J, et al. 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. 2000;18:3038–51.PubMedGoogle Scholar
  13. 13.
    Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106:2258–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Ascioglu S, et al. The invasive fungal infections cooperative group of the european organization for research and treatment of cancer and mycoses study group of the national institute of allergy and infectious diseases. Defining opportunistic invasive fungal Infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14.PubMedCrossRefGoogle Scholar
  15. 15.
    Jagarlamudi R, et al. Infections in acute leukemia: an analysis of 240 febrile episodes. Med Oncol. 2000;17:111–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Varaiya A, Kulkarni M, Bhalekar P, Dogra J. Incidence of carbapenem-resistant Pseudomonas aeruginosa in diabetes and cancer patients. Indian J Med Microbiol. 2008;26:238–40.PubMedCrossRefGoogle Scholar
  17. 17.
    Winston DJ, Ho WG, Bruckner DA, Gale RP, Champlin RE. Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients. Am J Med. 1988;85:21–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Mortimer J, Miller S, Black D, Kwok K, Kirby WM. Comparison of cefoperazone and mezlocillin with imipenem as empiric therapy in febrile neutropenic cancer patients. Am J Med. 1988;85:17–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Winston DJ, Ho WG, Bruckner DA, Champlin RE. Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone. Ann Intern Med. 1991;115:849–59.PubMedGoogle Scholar
  20. 20.
    Bodey G, Abi-Said D, Rolston K, Raad I, Whimbey E. Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients. Eur J Clin Microbiol Infect Dis. 1996;15:625–34.PubMedCrossRefGoogle Scholar
  21. 21.
    Lazarus HM, et al. Cefoperazone/sulbactam versus cefoperazone plus mezlocillin: empiric therapy for febrile, neutropenic bone marrow transplant patients. Int J Antimicrob Agents. 1996;7:85–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Winston DJ, Bartoni K, Bruckner DA, Schiller GJ, Territo MC. Randomized comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile granulocytopenic patients. Clin Infect Dis. 1998;26:576–83.PubMedCrossRefGoogle Scholar
  23. 23.
    Chandrasekar PH. Safety and efficacy of cefoperazone plus sulbactam versus ceftazidime in the empiric treatment of febrile neutropenia. J Pharm Technol. 1998;14:63–9.Google Scholar
  24. 24.
    Ozyilkan O, Yalçintaş U, Başkan S. Imipenem-cilastatin versus sulbactam-cefoperazone plus amikacin in the initial treatment of febrile neutropenic cancer patients. Korean J Intern Med. 1999;14:15–9.PubMedGoogle Scholar
  25. 25.
    Ziglam HM, Gelly K, Olver W. A survey of the management of neutropenic fever in oncology units in the UK. Int J Antimicrob Agents. 2007;29:430–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Indranil Ghosh
    • 1
  • Vinod Raina
    • 1
  • Lalit Kumar
    • 1
  • Atul Sharma
    • 1
  • Sameer Bakhshi
    • 1
  • Sanjay Thulkar
    • 2
  • Arti Kapil
    • 3
  1. 1.Department of Medical Oncology, Dr B.R.A. Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of Radiodiagnosis, Dr B.R.A. Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of MicrobiologyAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations