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Annu. Rev. Med. 2004. 55:519–26 doi: 10.1146/annurev.med.55.091902.103826 c 2004 by Annual Reviews. All rights reserved Copyright ° First published online as a Review in Advance on Oct. 15, 2003
MANAGEMENT OF INFECTIONS IN THE NEUTROPENIC PATIENT
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Kenneth V.I. Rolston Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030; email:
[email protected]
Key Words risk assessment, bacterial/fungal infections, empiric therapy, infection prevention ■ Abstract Neutropenic patients continue to be at increased risk for developing serious infections despite substantial advances in supportive care. Epidemiologic shifts occur periodically and need to be detected early because they influence prophylactic, empiric, and specific therapy strategies. Although effective in preventing bacterial and some fungal infections, prophylaxis must be used with caution because it is associated with the emergence of resistance. The choices for empiric therapy include combination regimens and monotherapy. Specific choices depend on local factors (epidemiology, susceptibility/resistance patterns, availability). Various treatment settings (hospitalbased, early discharge, outpatient) are also available, and the choice depends on the patient’s risk category. Early diagnosis and treatment of many fungal and viral infections remains suboptimal. Infection control and prevention are important strategies, especially with the emergence of multidrug-resistant organisms.
INTRODUCTION It has been four decades since Bodey et al. first described the relationship between neutropenia and infection (1). Although the risk of infection increases when the absolute neutrophil count (ANC) falls below 1000/mm3, the currently accepted definition of neutropenia is an ANC of ≤500/mm3 (2). The severity and duration of neutropenia are both important and influence not only the frequency and severity of infection but also the response to therapy and overall outcome. It has been estimated that all patients who have severe neutropenia (10–14 days). Antifungal prophylaxis (e.g., fluconazole/itraconazole) has been shown to reduce the frequency of infections caused by Candida spp. (22, 23). Mold infections are much more difficult to prevent, and effective strategies are yet to be developed. Some of the newer antifungal agents with activity against filamentous fungi (e.g., voriconazole, posaconazole) are being evaluated for the prevention of fungal infections.
SUMMARY The management of febrile neutropenic patients has evolved considerably. Although hospital-based, empiric therapy remains the standard for high-risk patients, newer strategies such as early discharge or oral, out-patient therapy are becoming the norm for low-risk patients. The most important factors for the selection of antimicrobial agents for empiric use are local microbiology and susceptibility/ resistance patterns. Better strategies for infection prevention are needed, particularly for fungal and viral infections. These issues will continue to challenge clinicians caring for febrile neutropenic patients for the foreseeable future. The Annual Review of Medicine is online at http://med.annualreviews.org
LITERATURE CITED 1. Bodey GP, Buckley M, Sathe YS, et al. 1966. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann. Intern. Med. 64:328–40 2. Hughes WT, Armstrong D, Bodey GP, et al. 2002. 2002 Guidelines for the use of an-
timicrobial agents in neutropenic patients with cancer. Clin. Infect. Dis. 34:730–51 3. Rolston KVI, Bodey GP. 2003. Infections in patients with cancer. In Cancer Medicine, ed. JF Holland, E Frei, pp. 2633–58. Ontario: BC Decker. 6th ed. 4. Rolston KVI. 1998. Expanding the options
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ROLSTON for risk-based therapy in febrile neutropenia. Diagn. Microbiol. Infect. Dis. 31:411– 16 Sickles EA, Greene WH, Wiernik PH. 1975. Clinical presentation of infection in granulocytopenic patients. Arch. Intern. Med. 135:715–19 Gomez L, Martino R, Rolston KV. 1998. Neutropenic enterocolitis: spectrum of the disease and comparison of definite and possible cases. Clin. Infect. Dis. 27:695– 99 Rolston KVI, Bodey GP. 1993. Diagnosis and management of perianal and perirectal infection in the granulocytopenic patient. In Current Clinical Topics in Infectious Diseases, ed. J Remington, MN Swartz, pp. 164–71. Boston: Blackwell Sci. Rolston K. 1999. New trends in patient management: risk-based therapy for febrile patients with neutropenia. Clin. Infect. Dis. 29:515–21 Talcott JA, Siegel RD, Finberg R, et al. 1992. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J. Clin. Oncol. 10:316–22 Klastersky J, Paesmans M, Rubenstein E, et al. 2000. The MASCC Risk Index: a multinational scoring system to predict low-risk febrile neutropenic cancer patients. J. Clin. Oncol. 18:3038–51 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– 94 Elting LS, Bodey GP, Fainstein V. 1986. Polymicrobial septicemia in the cancer patient. Medicine 65:2l8–25 Jones RN. 1999. Contemporary antimicrobial susceptibility patterns of bacterial pathogens commonly associated with febrile patients with neutropenia. Clin. Infect. Dis. 29:495–502 Rolston KVI, Kontoyiannis DP, Raad II, et al. 2003. Susceptibility surveillance among gram-negative bacilli at a compre-
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Annual Review of Medicine Volume 55, 2004
CONTENTS Effect of Completed Human Genome Sequence on Development of Novel Therapeutics for Human Disease, Christopher P. Austin Toward Alzheimer Therapies Based on Genetic Knowledge, John Hardy
Annu. Rev. Med. 2004.55:519-526. Downloaded from arjournals.annualreviews.org by "UNIV. OF WISCONSIN, MADISON" on 03/11/05. For personal use only.
Inherited Diseases Involving G Proteins and G Protein--Coupled Receptors, Allen M. Spiegel, Lee S. Weinstein The Scientific Basis for the Current Treatment of Parkinson's Disease, C. Warren Olanow Progress in Antisense Technology, Stanley T. Crooke Serum Proteomics in the Early Diagnosis of Cancer, Kevin P. Rosenblatt, Peter Bryant-Greenwood, J. Keith Killian, Arpita Mehta, David Geho, Virginia Espina, Emanuel F. Petricoin, Lance A. Liotta Molecular Neurobiology of Drug Addiction, Jennifer Chao, Eric J. Nestler Beta Cell Replacement for Type 1 Diabetes, Peter G. Stock, Jeffrey A. Bluestone Cochlear Implantation for the Treatment of Deafness, Benjamin J. Copeland, Harold C. Pillsbury Drug-Eluting Stents, T. Cooper Woods, Andrew R. Marks New Approaches to Hemodialysis, Andreas Pierratos Emerging Infectious Threats to the Blood Supply, Roger Y. Dodd, David A. Leiby Lead Poisoning, Herbert Needleman The Impact of Minimally Invasive Surgical Techniques, Sir Ara Darzi, Yaron Munz Implementing a Research Agenda for Complementary and Alternative Medicine, Jonathan D. Berman, Stephen E. Straus Basic Advances and New Avenues in Therapy of Spinal Cord Injury, Bruce H. Dobkin, Leif A. Havton Clinical Management of Tuberculosis in the Context of HIV, Bouke C. de Jong, Dennis M. Israelski, Elizabeth L. Corbett, Peter M. Small HIV-Associated Lipodystrophy: Pathogenesis, Prognosis, Treatment, and Controversies, Polyxeni Koutkia, Steven Grinspoon Human Papillomavirus Vaccines and Prevention of Cervical Cancer, Kathrin U. Jansen, Alan R. Shaw Opportunities for Control of Meningococcal Disease in the United States, Pratima L. Raghunathan, Scott A. Bernhardt, Nancy E. Rosenstein Recent Advances in the Development of HIV-1 Vaccines Using Replication-Incompetent Adenovirus Vectors, John W. Shiver, Emilio A. Emini Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure, William H. Gaasch, Michael R. Zile Mechanisms of Pulmonary Fibrosis, Victor J. Thannickal, Galen B. Toews, Eric S. White, Joseph P. Lynch III, Fernando J. Martinez Systemic Mastocytosis, Cem Akin, Dean D. Metcalfe
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The erbB Family: Targets for Therapeutic Development Against Cancer and Therapeutic Strategies Using Monoclonal Antibodies and Tyrosine Kinase Inhibitors, Eric K. Rowinsky Nonmyeoablative Immunotherapy for Solid Tumors, Richard W. Childs, John Barrett Rituximab: Expanding Role in Therapy for Lymphomas and Autoimmune Diseases, William Rastetter, Arturo Molina, Christine A. White
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Botulinum Toxin and Other New Approaches to Migraine Therapy, Avi Ashkenazi, Stephen D. Silberstein Management of Infections in the Neutropenic Patient, Kenneth V.I. Rolston
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