Correspondence

Fever in Immunocompromised Patients

N Engl J Med 2000; 342:217-218January 20, 2000

Article

To the Editor:

Pizzo, in his review entitled “Fever in Immunocompromised Patients” (Sept. 16 issue),1 states that immediate postoperative care for recipients of bone marrow transplants should be similar to the treatment of high-risk patients with cancer and that either single-agent or multiple-agent parenteral antibiotic therapy can be chosen. Single-agent antimicrobial therapy has not been well studied in recipients of bone marrow transplants, especially patients undergoing allogeneic transplantation. For instance, in the application submitted to the Food and Drug Administration for cefepime to be used as monotherapy for fever and neutropenia, more than 1200 patients with fever and neutropenia were described, of whom only 60 had received any type of bone marrow transplant.2

Similarly, data are lacking on the efficacy of single-agent therapy with either ceftazidime or imipenem–cilastatin in this setting. This is a concern especially because of the increased incidence of bacteremia and death due to viridans streptococcus in recipients of bone marrow transplants3 and because of evidence that the activity of ceftazidime is questionable in this setting.4 Moreover, in recipients of autologous or allogeneic bone marrow transplants, severe mucositis often develops as a result of the conditioning regimen. The Infectious Diseases Society of America recently stated that patients with mucositis who have fever and neutropenia should be treated with a combination of vancomycin and ceftazidime.5 Thus, there is not sufficient information in the current literature to support the administration of a single antimicrobial agent to recipients of bone marrow transplants at the onset of fever and neutropenia.

Finally, there are data that show that the sensitivity of high-resolution computed tomography (CT) is significantly increased in the diagnosis of pneumonia in patients with persistent fever who have undergone bone marrow transplantation.6 Since plain chest radiography has a very poor negative predictive value in these patients, high-resolution CT scans should be included in the evaluation of any transplant recipient who has persistent fever and neutropenia.

Jonathan S. Serody, M.D., Ph.D.
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

6 References

1. 1

   Pizzo PA. Fever in immunocompromised patients. N Engl J Med 1999;341:893-900
   Full Text | Web of Science | Medline

2. 2

   Application to the FDA for cefepime for the indication of monotherapy in the treatment of fever and neutropenia, April 1997.
   

3. 3

   Bilgrami S, Feingold JM, Dorsky D, Edwards RL, Clive J, Tutschka PJ. Streptococcus viridans bacteremia following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1998;21:591-595
   CrossRef | Web of Science | Medline

4. 4

   Rolston KV, Berkey P, Bodey GP, et al. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Arch Intern Med 1992;152:283-291
   CrossRef | Web of Science | Medline

5. 5

   Hughes WT, Armstrong D, Bodey GP, et al. 1997 Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clin Infect Dis 1997;25:551-573
   CrossRef | Web of Science | Medline

6. 6

   Heussel CP, Kauczor HU, Heussel GE, et al. Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell transplant recipients: use of high-resolution computed tomography. J Clin Oncol 1999;17:796-805
   Web of Science | Medline

Author/Editor Response

Dr. Pizzo replies:

To the Editor: It is important to differentiate between evidence-based principles and the preferences of clinical practice. Patients undergoing allogeneic or autologous bone marrow transplantation initially resemble high-risk patients with neutropenia. However, in some institutional settings, or after certain chemotherapy regimens, the risk of a primary or secondary infection not treatable with a third- or fourth-generation cephalosporin or carbapenem must be considered. Serody is correct in cautioning that certain recipients of bone marrow transplants may be at risk for specific infections (such as those due to alpha-hemolytic streptococci) that would necessitate additional therapy (e.g., with vancomycin). However, this recommendation does not apply to every patient with oral mucositis or to all transplant recipients, unless the prevalence at a specific institution justifies the risks associated with empirical vancomycin therapy. Appropriately controlled clinical trials in specific populations should guide such recommendations.

I agree with Serody about the potential benefit of high-resolution CT scanning of the chest in diagnosing pneumonia (such as that associated with aspergillus) in patients with persistent or recurrent fever and in patients who have neutropenia for more than 7 to 10 days. However, this is not unique to recipients of bone marrow transplants and applies to all high-risk patients with neutropenia. This might be considered a principle as well as a preference.

Philip A. Pizzo, M.D.
Children's Hospital, Boston, MA 02115

Citing Articles (6)

Citing Articles

1. 1

   Mario Tumbarello, Teresa Spanu, Morena Caira, Enrico M. Trecarichi, Luca Laurenti, Eva Montuori, Luana Fianchi, Fiammetta Leone, Giovanni Fadda, Roberto Cauda, Livio Pagano. (2009) Factors associated with mortality in bacteremic patients with hematologic malignancies. Diagnostic Microbiology and Infectious Disease 64:3, 320-326
   CrossRef

2. 2

   Enrico M. Trecarichi, Mario Tumbarello, Teresa Spanu, Morena Caira, Luana Fianchi, Patrizia Chiusolo, Giovanni Fadda, Giuseppe Leone, Roberto Cauda, Livio Pagano. (2009) Incidence and clinical impact of extended-spectrum-β-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies. Journal of Infection 58:4, 299-307
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3. 3

   G BEARMAN, R WENZEL. (2005) Bacteremias: A Leading Cause of Death. Archives of Medical Research 36:6, 646-659
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4. 4

   Hilmar Wisplinghoff, Oliver A. Cornely, Susanne Moser, Ullrich Bethe, Hartmut Stutzer, Bernd Salzberger, Gerd Fatkenheuer, Harald Seifert. (2003) Outcomes of Nosocomial Bloodstream Infections in Adult Neutropenic Patients: A Prospective Cohort and Matched Case —Control Study • . Infection Control and Hospital Epidemiology 24:12, 905-911
   CrossRef

5. 5

   Hilmar Wisplinghoff, Harald Seifert, Richard P. Wenzel, Michael B. Edmond. (2003) Current Trends in the Epidemiology of Nosocomial Bloodstream Infections in Patients with Hematological Malignancies and Solid Neoplasms in Hospitals in the United States. Clinical Infectious Diseases 36:9, 1103-1110
   CrossRef

6. 6

   Georg Maschmeyer. (2001) Pneumonia in febrile neutropenic patients: radiologic diagnosis. Current Opinion in Oncology 13:4, 229-235
   CrossRef