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INTRODUCTION

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SUMMARY

Infection is a major cause of morbidity and mortality in patients with severe inherited or acquired neutropenia or aplastic anemia, qualitative disorders of neutrophils, and, notably, those persons receiving chemotherapy for treatment of hematologic neoplasms. Severe neutropenia and monocytopenia often result from the combined effects of replacement of marrow with malignant cells and superimposed intense chemotherapy. The severity and duration of the neutropenia determine the risk of infection. Bacterial infections may result in rapid clinical deterioration and even death. Fungal, viral, and parasitic infections also may result in potentially lethal complications during or after chemotherapy. This chapter considers methods of diagnosis of bacterial, fungal, viral, and protozoal infection and describes treatment regimens. Because prevention of infection during periods of neutropenia should reduce morbidity and improve outcome, attention is focused on prophylaxis against bacterial, parasitic, viral, and/or fungal infections.

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RISK FACTORS AND INFECTING ORGANISMS

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SEVERITY OF NEUTROPENIA

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Bacterial, fungal, viral, and parasitic organisms may cause infection in neutropenic patients.1 Bacterial infections are the most frequent and usually the most serious. The risk for bacterial infection increases when the neutrophil count falls to less than 0.5 × 109/L and becomes especially pronounced at neutrophil counts less than 0.1 × 109/L.1 The rate of decline and duration of neutropenia are important in determining the risk of bacterial infection. Disruption of mucosal barriers, especially in the oral cavity, esophagus, and bowel, further favors the development of infection by providing portals of entry.

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Acronyms and Abbreviations:

CMV, cytomegalovirus; CT, computed tomography; ESBL, extended-spectrum β-lactamase; Ig, immunoglobulin; IVIG, intravenous immunoglobulin; LFT, liver function test; MRSA, methicillin-resistant Staphylococcus aureus; PCP, Pneumocystis jiroveci pneumonia; RSV, respiratory syncytial virus; VRE, vancomycin-resistant Enterococcus.

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BACTERIAL PATHOGENS

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Historically, Gram-negative bacilli have been the most commonly isolated pathogens. These organisms include Klebsiella, Escherichia coli, Pseudomonas, and Proteus. These bacteria are responsible for a variety of infections, including pneumonia, soft-tissue infections, perirectal infections, and bacteremia. Urinary tract infections are less frequent unless a urinary catheter is present or urinary tract obstruction has developed. Meningitis is uncommon.

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At present, roughly half of all documented infections in neutropenic patients are caused by Gram-positive pathogens. This likely results from the popularity of semipermanent venous catheters and from the use of prophylactic regimens that are active against Gram-negative rods. Staphylococcal species and Enterococcus are now the pathogens most frequently isolated from neutropenic patients.2 Several reports document the increasing frequency of viridans group streptococci as a major pathogen in neutropenic patients, especially in those receiving a hematopoietic stem cell transplant, perhaps because these patients have a higher incidence of mucositis.3 Among infections caused by both Gram-negative and Gram-positive organisms, antibiotic resistance is a growing problem and is discussed under “Bacterial Infections” below. Anaerobic infections are less common unless periodontal or gastrointestinal pathology ...

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