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, 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 and viral infections also may result in potentially lethal complications during or after chemotherapy. This chapter considers methods of diagnosis of bacterial, fungal, and viral infections and describes treatment regimens. Because prevention of infection during periods of neutropenia can reduce morbidity and improve outcome, attention is focused on prophylaxis strategies against bacterial, viral, and fungal infections.
Acronyms and Abbreviations
ANC, absolute neutrophil count; BAL, bronchoalveolar lavage; CISNE, Clinical Index of Stable Febrile Neutropenia; CMV, cytomegalovirus; CRE, carbapenem-resistant Enterobacteriaceae; CT, computed tomography; ESBL, extended-spectrum β-lactamase; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; LFT, liver function test; HIV, human immunodeficiency virus; PCR, polymerase chain reaction; MASCC, Multinational Association of Supportive Care in Cancer; MRSA, methicillin-resistant Staphylococcus aureus; PCP, Pneumocystis jiroveci pneumonia; RSV, respiratory syncytial virus; VRE, vancomycin-resistant Enterococcus; VZV, varicella zoster virus.
RISK FACTORS AND INFECTING ORGANISMS
Patients with neutropenia are at risk for a range of infections caused by bacterial, fungal, viral, and parasitic organisms.1,2 Bacterial infections are the most frequent and usually the most serious. The degree and duration of neutropenia are important in determining the risk of bacterial infection, which increases when severe neutropenia develops in patients, defined as an absolute neutrophil count (ANC) of <0.5 × 109/L, and becomes especially pronounced when the ANC falls below 0.2 cells × 109/L (profound neutropenia).3 Specifically, disruption of mucosal barriers along the gastrointestinal tract (oral cavity, esophagus, and bowel) provide portals of entry for the patient’s endogenous microbial flora to cause invasive disease.
Up until the 1980s, gram-negative bacilli such as Klebsiella, Escherichia coli, Proteus, and Pseudomonas were the most commonly isolated pathogens among neutropenic patients,4 causing a range of infections including bacteremia, pneumonia, soft-tissue infections, and perirectal infections. Less frequent sources of gram-negative infections are urinary tract infections, which occur more commonly when a urinary catheter or urinary tract obstruction is present, and meningitis.
Currently, a little more than half of all documented infections in neutropenic patients are caused by gram-positive pathogens.2,5,6 This change likely resulted from the popularity of semipermanent venous catheters and from the use of prophylactic regimens that are active against gram-negative rods. Of gram-positive pathogens, coagulase-negative staphylococci are the most common, though it is important to note ...